Category Archives: Stem Cells

Aileron Therapeutics, Inc.

New ex vivo data demonstrates protection against cyclophosphamide-induced damage to hair follicles and their stem cells

Encore presentation of data presented at Society for Investigative Dermatology in May 2022 shows:

ALRN-6924 temporarily arrested the cell cycle in human scalp hair follicles and their stem cells

Ex vivo data demonstrated protection against taxane-induced damage to hair follicles and their stem cells

Nearly all breast cancer patients receiving neoadjuvant or adjuvant chemotherapy, including cyclophosphamide and taxanes, such as docetaxel, experience alopecia (hair loss)

Aileron is evaluating ALRN-6924 as a novel chemoprotective agent to prevent chemotherapy-induced bone marrow toxicities and alopecia in its ongoing Phase 1b breast cancer trial

BOSTON, Sept. 30, 2022 (GLOBE NEWSWIRE) -- Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives, today announced an oral presentation at the European Society for Dermatological Research (ESDR) Annual Meeting, taking place September 28 October 1, 2022 in Amsterdam.

This presentation includes non-clinical data initially presented at the Society for Investigative Dermatology in May 2022 as well as new non-clinical data developed in collaboration with Professor Ralf Paus, M.D., DSc, FRSB and his colleagues at the Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery at the University of Miami Miller School of Medicine.

Details of the presentation are as follows:

Title:

Temporary cell cycle arrest in human scalp hair follicles and their epithelial stem cells by ALRN-6924: A novel strategy to selectively protect p53-wildtype cells against paclitaxel-induced alopecia [Abstract 549]

Presenter:

Dr. Ralf Paus; Paus Laboratory, University of Miami Miller School of Medicine

Date:

Saturday, October 1, 2022

Time:

12:40 12:50 p.m. (local time)

Session:

Concurrent session #9: Photobiology and Pigmentation

Until one is confronted personally with the loss of hair due to chemotherapy, I think its difficult to truly understand just how difficult this side effect can be for patients. It is yet another burden layered on top of their already-daunting fight against cancer, said Dr. Paus. Cold caps, the only FDA-approved treatment for chemotherapy-induced alopecia, are unavailable in many institutions, can cause additional discomfort, and while often quite useful are of unpredictable efficacy in a given individual patient. One also cannot help wondering whether scalp micro-metastases might profit from scalp cooling.

Story continues

Dr. Paus continued, Based on our hair follicle and scalp skin organ culture work with ALRN-6924, testing two of the most hair loss-inducing chemotherapies, paclitaxel and cyclophosphamide, were very encouraged by the potential this drug may hold to prevent alopecia in cancer patients, including for protecting the hair follicle's sensitive stem cell compartment from permanent damage. Were particularly excited by ALRN-6924s highly innovative design, which selectively protects normal cells from the destructive effects of chemotherapy, but in contrast to any other currently available alopecia-protective strategy crucially, not the cancer cells.

Aileron is currently developing ALRN-6924, a first-in-class MDM2/MDMX dual inhibitor, to selectively protect healthy cells in patients with cancers that harbor p53 mutations to reduce or eliminate chemotherapy-induced side effects while preserving chemotherapys attack on cancer cells. The company is conducting a Phase 1b clinical trial of ALRN-6924 in patients with p53-mutated breast cancer undergoing either neoadjuvant or adjuvant treatment with docetaxel, doxorubicin and cyclophosphamide, also known as TAC. Ailerons vision is to bring chemoprotection to all patients with p53-mutated cancer regardless of the type of cancer or chemotherapy.

Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron, commented, Were excited about the results generated by Dr. Paus and his colleagues, particularly given their significant and widely recognized expertise in chemotherapy-induced alopecia. We have amassed a body of strong scientific evidence, including the data being presented at the ESDR meeting, which demonstrate ALRN-6924s cell cycle arrest mechanism and support its potential to protect against chemotherapy-induced bone marrow toxicities and other toxicities, including alopecia. Collectively, these nonclinical and clinical data have informed the design of our breast cancer trial. We look forward to our anticipated data readouts from that trial later this year and into 2023.

About the Paus et al. Findings

Taxanes, such as paclitaxel and docetaxel, are known to cause severe and often permanent chemotherapy-induced alopecia. Over 90% of patients treated with this chemotherapy class experience alopecia, and approximately 10% (paclitaxel) to 25% (docetaxel) of patients experience permanent alopecia. Cyclophosphamide is also known to cause alopecia: it is commonly co-administered with doxorubicin (Adriamycin) chemotherapy in the AC combination, with greater than 90% of patients experiencing hair loss.

Dr. Paus and his team previously demonstrated that paclitaxel damages human scalp hair follicles by inducing massive mitotic defects and apoptosis in hair matrix keratinocytes as well as bulge stem cell DNA damage, and that pharmacological induction of transient cell cycle arrest can protect hair follicles and stem cells (Purba et al. EMBO Molecular Medicine 2019). Aileron previously conducted in vitro studies showing that ALRN-6924 protected human fibroblasts in cell culture from multiple chemotherapies, but not p53-mutant breast cancer cells.

In the non-clinical findings presented at the ESDR and SID meetings, when organ-cultured anagen (i.e., active growth phase) scalp hair follicles from human donors were pre-treated with ALRN-6924 or vehicle (i.e., placebo), followed by paclitaxel or vehicle, ALRN-6924 significantly increased the number of p21-positive hair matrix keratinocytes and bulge stem cells compared to vehicle or paclitaxel alone, confirming cell cycle arrest ex vivo. Further, pretreatment of paclitaxel-treated human hair follicles with ALRN-6924, led to a reduction in the number of melanin clumps, a marker of hair follicle cytotoxicity and dystrophy, as well as a reduction in apoptosis, pathological mitosis, and DNA damage. In new data presented at the ESDR meeting, these assays also yielded positive findings for 4-HC (4-hydroperoxy cyclophosphamide), the active metabolite of cyclophosphamide that is formed in vivo and commonly used for in vitro studies. Aileron believes that these findings support clinical investigation of ALRN-6924s ability to prevent both acute and permanent chemotherapy-induced alopecia, in addition to its ongoing evaluation of ALRN-6924s ability to protect against chemotherapy-induced bone marrow and other toxicities.

About Ailerons Breast Cancer Clinical Trial

Aileron is underway with a Phase 1b, open-label, single-arm, multicenter trial designed to evaluate the safety, tolerability and chemoprotective effect of ALRN-6924 in up to 24 patients with p53-mutated breast cancer undergoing either neoadjuvant or adjuvant treatment with docetaxel, doxorubicin and cyclophosphamide, also known as TAC. The primary endpoints are duration and incidence of severe neutropenia (Grade 4) in cycle 1. Secondary endpoints include the chemoprotective effect of ALRN-6924 on chemotherapy-induced alopecia, as well as other hematologic and non-hematologic toxicities. Planned readouts from the breast cancer trial include data from initial patients in the trial in the fourth quarter of 2022; an interim analysis on 12 patients in the second quarter of 2023; and topline results from 20 patients in the third quarter of 2023.

About Aileron Therapeutics

Aileron is a clinical stage chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives. ALRN-6924, our first-in-class MDM2/MDMX dual inhibitor, is designed to activate p53, which in turn upregulates p21, a known inhibitor of the cell replication cycle. ALRN-6924 is the only reported chemoprotective agent in clinical development to employ a biomarker strategy, in which we exclusively focus on treating patients with p53-mutated cancers. Our targeted strategy is designed to selectively protect multiple healthy cell types throughout the body from chemotherapy without protecting cancer cells. As a result, healthy cells are spared from chemotherapeutic destruction while chemotherapy continues to kill cancer cells. By reducing or eliminating multiple chemotherapy-induced side effects, ALRN-6924 may improve patients quality of life and help them better tolerate chemotherapy. Enhanced tolerability may result in fewer dose reductions or delays of chemotherapy and the potential for improved efficacy.

Our vision is to bring chemoprotection to all patients with p53-mutated cancers, which represent approximately 50% of cancer patients, regardless of type of cancer or chemotherapy. Visit us at aileronrx.com to learn more.

Forward-Looking Statements

Statements in this press release about Ailerons future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements about the potential of ALRN-6924 as a chemoprotective agent and the Companys strategy and clinical development plans. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, would and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Ailerons cash resources will be sufficient to fund its continuing operations for the periods anticipated or with respect to the matters anticipated; whether initial results of clinical trials will be indicative of final results of those trials or results obtained in future clinical trials, including trials in different indications; whether ALRN-6924 will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will be accepted by and warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether ALRN-6924 will receive approval from regulatory agencies on a timely basis or at all or in which territories or indications ALRN-6924 may receive approval; whether, if ALRN-6924 obtains approval, it will be successfully distributed and marketed; what impact the coronavirus pandemic may have on the timing of our clinical development, clinical supply and our operations; and other factors discussed in the Risk Factors section of Ailerons annual report on Form 10-K for the year ended December 31, 2021, filed on March 28, 2022, and quarterly report on Form 10-Q for the quarter ended June 30, 2022, filed on August 15, 2022,and risks described in other filings that Aileron may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Aileron specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise.

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Aileron Therapeutics Announces Oral Presentation of Non-Clinical Data Demonstrating ALRN-6924 Protected Human Hair Follicles and Their Stem Cells from...

New therapies have improved outcomes for patients in frontline treatment for Hodgkin lymphoma, and research now is addressing how subsequent therapies can meet needs of patients who progress after early lines of treatment.

When a patient has progressed through chemotherapytheyve had a stem cell transplant, theyve had brentuximab vedotin [Adcetris; Seagen] and theyve had PD-1 blockade, [physicians] are unsure of what treatments are available, Alex F. Herrera, MD, associate professor in the Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation at City of Hope in Duarte, California, said in an interview with The SOHO Daily News before the Tenth Annual Meeting of the Society of Hematologic Oncology (SOHO 2022).

Most patients with Hodgkin lymphoma can be cured by chemotherapy and radiotherapy, but the 20% to 25% of patients who do not respond can be as difficult to treat as those with other cancers, says Herrera. This means reducing the number of patients who relapse is crucial. Two major breakthroughs in this setting have been the introduction of brentuximab vedotin and PD-1 blockade, both of which have advanced to being used in the early lines of therapy in the United States. As the standard becomes using novel agents like brentuximab vedotin in frontline therapy, and maybe someday PD-1 blockade in frontline therapy, it even makes this a more pressing need to find therapies that work after a patient has progressed on those therapies, Herrera says.

Herreras presentation at SOHO 2022 discusses approaches to subsequent therapy for patients who have received brentuximab vedotin and PD-1 blockade. He says that although they have improved the outcomes of patients with Hodgkin lymphoma, patients who are not cured by initial therapies are now often resistant to these treatments as well. More durable responses are also needed for those who do benefit from these therapies, since it is a minority of patients who will have a long-term durable response from these immunotherapies when they are used alone.

Hodgkin lymphoma is a disease that typically affects younger patients, says Herrera. If a patient is resistant to therapy, our goal is to be able to not just get a patient in response, but [to keep] a patient in response for as long as we can.

A wide range of options could offer survival benefit to patients with relapsed disease. Because few new agents have been approved for patients with relapsed disease after brentuximab vedotin and PD-1 blockade, clinical trials play a major role in offering patients the best available care.

Emerging Therapies

New agents such as antibody-drug conjugates (ADCs) could offer a next-line approach. Whereas brentuximab vedotin targets CD30, camidanlumab tesirine (ADCT-301) is another ADC that targets CD25, which is also located on or around Hodgkin lymphoma cells. A phase 2 trial (NCT04052997) is investigating this ADC in patients who previously received brentuximab vedotin and an antiPD-1 agent.

Extending the length of benefit from antiPD-1 agents and overcoming resistance to immune checkpoint inhibitors is an important area of investigation due to the major role antiPD-1 agents now play in treating Hodgkin lymphoma. One potential approach is combining PD-1 blockade with an epigenetic-based or other targeted therapy. These include hypomethylating agents such as decitabine and azacitidine as well as histone deacetylase inhibitors such as vorinostat (Zolinza; Merck) and entinostat.

A study conducted in China (NCT03250962, NCT02961101) showed a significantly longer duration of response and favorable efficacy with the addition of decitabine to the antiPD-1 agent camrelizumab for patients with Hodgkin lymphoma who were PD-1 nave as well as those who were resistant to prior antiPD-1 therapy.1,2 Herrera is helping lead a similar study (NCT05162976) at City of Hope evaluating azacitidine plus nivolumab (Opdivo; Bristol Myers Squibb) to assess how a hypomethylating agent can improve response to immunotherapy. He is also the principal investigator of a phase 1 study (NCT03150329) of vorinostat (Zolinza; Merck) combined with pembrolizumab (Keytruda; Merck) in patients with Hodgkin lymphoma and other lymphoma types.

Herrera says targeted therapy that can extend the duration of benefit from immunotherapy would be an ideal approach in patients with low disease burden or fewer symptoms, because they are not in need of a fast-acting regimen and can benefit from the greater tolerability of immunotherapy. When a patient is resistant to immunotherapy, if we can re-sensitize them with something thats reasonably well tolerated and get them another year or two of response, [and] buy them that time, that might be a valuable option, he says.

For patients with higher disease burden who are more heavily symptomatic, chemotherapy may be the best approach to get a strong, rapid response. Research has also shown that PD-1 blockade can cause patients to become more sensitive to subsequent treatments,3 meaning chemotherapy could be used in combination with immunotherapy or afterward in patients who previously progressed on therapies such as the ABVD combination regimen (doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine).

Drugs already in use such as lenalidomide (Revlimid; Bristol Myers Squibb), everolimus (Afinitor; Novartis), and temsirolimus (Torisel; Pfizer) can also have a role as subsequent therapies when patients need to achieve a strong anticancer response to improve their outcomes, according to Herrera.

Cellular Therapies

Cellular therapies such as chimeric antigen receptor (CAR) T-cell therapy have made an impact in non-Hodgkin lymphoma and other hematologic malignancies, providing long-term durable remissions in many patients who had few options remaining. Herrera says CD30-targeted CAR T-cell therapies are promising for Hodgkin lymphoma, although they are not yet approved, and several CAR T-cell trials such as the phase 2 CHARIOT study (NCT04268706) are under way. A lingering question for him is whether CAR T-cell products will lead to durable responses in the relapsed population that is resistant to chemotherapy, immunotherapy, and CD30-targeted ADCs.

Herrera says he and his colleagues look for patients who may benefit from trials of cellular therapies that evaluate CAR T cells or natural killer T cells that can result in a durable response. We are trying to refer patients [to trials] or give patients these types of cellular therapies when they are available, he said.

Although the advances in the field have deemphasized the need for patients to receive an allogeneic stem cell transplant, Herrera anticipates it may still have a role as survival is now extended for patients who now may receive 5 or more prior lines of therapy. Four or 5 years later, then you have all these patients who are now progressing on these later-line therapies and they need something else, he says. I think understanding the role allogeneic stem cell transplant may play isa bit of an unresolved question that probably is going to need to be explored again.

There is a range of options available to patients. Theres a lot of drug development happening. And I think that early results are promising and exciting, Herrera says. My talk is about just opening that door and showing folks that theres a lot out there that were studying and that is possible.

REFERENCES:

1. Nie J, Wang C, Liu Y, et al. Addition of low-dose decitabine to anti-PD-1 antibody camrelizumab in relapsed/refractory classical Hodgkin lymphoma.J Clin Oncol. 2019;37(17):1479-1489. doi:10.1200/JCO.18.02151

2. Liu Y, Wang C, Li X, et al. Improved clinical outcome in a randomized phase II study of anti-PD-1 camrelizumab plus decitabine in relapsed/refractory Hodgkin lymphoma.J Immunother Cancer. 2021;9(4):e002347. doi:10.1136/jitc-2021-00234

3. Rossi C, Gilhodes J, Maerevoet M, et al. Efficacy of chemotherapy or chemo-anti-PD-1 combination after failed anti-PD-1 therapy for relapsed and refractory Hodgkin lymphoma: a series from Lysa centers. Am J Hematol. 2018;93(8):1042-1049. doi:10.1002/ajh.25154

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Research Shows Promise for Directing Later Lines of Therapy for Hodgkin Lymphoma - Targeted Oncology

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Hereditary E200K mutation within the prion protein gene alters human iPSC derived cardiomyocyte function | Scientific Reports - Nature.com

If this story piqued your interest, chances are you already know that the foods you eat impact your body. Eating is your greatest opportunity to take charge of your health because, well, you do it every day, three or more times a day. It's simple, and almost automatic, unlike working out.

What isn't so simple is making the right food choices among the hundreds of options in our refrigerators and pantries, grocery stores, and restaurants. That's why meal plans, menus, and curated lists can be so helpful in guiding us toward better health.

In his best-selling book Eat to Beat Disease: The New Science of How Your Body Can Heal Itself, physician-scientist Dr. William W. Li, MD, lays out a strategy called the 5 x 5 x 5 framework that provides readers with a structure to add beneficial foods into their diets rather than cutting foods out.

"Five defense systems form key pillars to your health and each system is influenced by diet," says Dr. Li, whose TED Talk, "Can We Eat to Starve Cancer," has received 11 million views. "The 5 x 5 x 5 framework is a strategy to support your body's five health defense systems by working a minimum of five health-supporting foods you already like to eat into five meal and snack opportunities a day."

The following are the five health defense systems and some of the common foods that make them stronger. Choose at least one food from each defense category to eat each day, says Dr. Li. (Note that many of the foods support multiple defense systems.)

Angiogenesis is the process our body uses to grow and maintain blood vessels. A healthy angiogenesis system is a defense mechanism that regulates where blood vessels should grow and can cut off the blood supply to tumors, according to Dr. Li. Certain foods can help your angiogenesis system remain in a healthy state of homeostasis. "You can eat to starve cancer, grow vessels to feed your heart, and stave off deadly diseases to live a longer, healthier life," he says.

Best supporting foods: almonds, apples, berries, broccoli, cabbage, chicken (dark meat), cinnamon, dark chocolate, green tea, licorice root, olive oil, pink grapefruit, pistachios, red wine, soy, tomatoes, tuna, watermelon, and more.

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Your body is constantly rebuilding. Powered by more than 750,000 stem cells throughout your bone marrow, lungs, liver, and almost every organ, your body regenerates itself every day. Some foods mobilize those cells to regenerate. Other foods can kill deadly stem cells that spark cancer growth.

Best Supporting Foods: apple peel, arctic char (and other good sources of fish oil), barley, black tea (and green tea), berries, carrots, celery, coffee, kiwifruit, onions, peanuts, purple potatoes, red-leaf lettuce, salmon, spinach, Swiss chard, turmeric, walnuts, whole grains, and more.

Our gut microbiome is a key defense system because "it controls our immune system, influences angiogenesis, and even helps produce hormones that influence our brain," says Dr. Li. But the system can quickly become unbalanced. Disturbances of the gut microbiome triggered by unhealthy eating patterns, environmental factors, and the use of antibiotics have been associated with serious health conditions like obesity, metabolic syndrome, type 2 diabetes, and many more. One way to help support our microbiome is to eat microbe-rich foods.6254a4d1642c605c54bf1cab17d50f1e

Best Supporting Foods: apricots, arugula, blueberries and other berries, broccoli, cabbage, cauliflower, collard greens, dark chocolate, flaxseed, kale, kimchi, mushrooms, oranges, pumpkin seeds, red wine, sauerkraut, turmeric, among others.

"Our DNA has surprising repair mechanisms that protect us against damage caused by solar radiation, chemicals, stress, poor sleep, and diet habits, among other insults," says Dr. Li. "Certain foods can prompt DNA to fix itself while others turn on helpful genes, turn off harmful ones, and lengthen our telomeres, which protect our DNA."

Best Supporting Foods: almond butter, basil, berries, bluefish, bok choy, cauliflower, coffee, flax seeds, grapefruit, green tea, kale, macadamia nuts, mangoes, nectarines, olive oil (EVOO), oysters, plums, salmon, sardines, soy, strawberries, tuna, turmeric, walnuts, among others.

The immune system is like a double-edged sword. It produces an army of cells that go out and defend us against the common cold and other simple infections as well as serious threats like the COVID-19 virus. On the flip side, when the immune system continues to attack even if you're not sick or injured, it can cause what's known as low-grade chronic inflammation that can damage our tissues over time. The right types of foods can support your immune system's ability to resist disease while reducing the damaging inflammation.

Best Supporting Foods: aged garlic, apples, arugula, Belgian endive, berries, broccoli rabe, chamomile tea, cherries, chia seeds, chili peppers, cranberries, dark chocolate, eggplant, flax seeds, green tea, kimchi, kale, mustard greens, olive oil (EVOO), pomegranates, red wine, sauerkraut, shiitake mushrooms, strawberries, Swiss chard, turmeric, turnips, white button mushrooms, among others.

To use Dr. Li's 5 X 5 X framework, pick your favorite foods from the above lists. Then select five foods to eat each day, making sure each one supports at least one of the defense systems. Also, be sure you're covering all five systems across these five food choices. You can eat all five foods you've chosen for the day as part of one meal or spread out through all five meals and snacks or other eating occasions over the course of the day. "Just make sure you get all five foods in each day," says Li. That'll guarantee that you're making clear strides toward improving your health.

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How To Eat Your Way to Better Health According to a Doctor - Eat This, Not That

MARLBOROUGH, Mass., Sept. 22, 2022 /PRNewswire/ -- Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company developing the next generation of therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, today announced that its research partner, Helmholtz Munich, presented preclinical data showing that Phio's lead clinicalproduct PH-762, an INTASYL compound targeting PD-1, increases the T cell population expressing stem cell-like characteristics, which in doing so, is expected to improve T cell persistence in vivo, therefore, resulting in enhanced duration of anti-tumor activity. These data were presented at the 9th Immunotherapy of Cancer Conference (ITOC) annual meeting, which is being held September 22 to 24, 2022 in Munich, Germany.

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"A well-known hurdle in adoptive cell therapy (ACT) with T cells is the poor persistence of effector T cells in patients, which are key players in killing tumor cells. These data demonstrate that PH-762 enhances the population of T cells that have more stem-like characteristics. As has been reported in literature, stem-like T cells are more resilient and result in an ACT product with prolonged tumor killing activity," said Dr. Simon Fricker, Phio's VP of Research and Development. "Increasing the frequency of this cell population by downregulating PD-1 using our PH-762 INTASYL compound is expected to enhance the population of T cells that fight cancer by increasing their proliferative activity, persistence, responsiveness and cell differentiation characteristics that are believed to improve the immune system's capacity to kill cancer cells."

"These new data complement the robust data set we've generated over the past several years for PH-762 in the treatment of melanoma by reducing the expression of PD-1, a clinically validated target for immunotherapy. Currently, Phio is conducting a first-in-human clinical trial of PH-762 to treat patients with advanced melanoma," concluded Dr. Fricker.

This preclinical study assessed the potential of PH-762 to downregulate PD-1 to increase the frequency of a CD8 T cell population with a stem-like associated marker profile. T cells were incubated with PH-762 and co-cultured with an autologous renal cell carcinoma tumor cell line. Results showed that PH-762 treatment reduced PD-1 surface expression in T cells compared to control and PH-762 mediated PD-1 silencing increased the population of T cells that expressed stem-like markers, including higher expression levels of certain surface markers that identify stem cell memory T cells.

ITOC is a European meeting providing a global platform for translational research in the field of immuno-oncology as well as a forum for discussion of early clinical translation and to address its unique challenges. The presentation detailing these data is titled, "RNAi mediated PD-1 knockdown induces a TCF-1 positive population in activated human CD8 T cells with stem-like associated marker profile."

About PH-762

PH-762 activates immune cells to better recognize and kill cancer cells by reducing the expression of PD-1, a clinically validated target for immunotherapy. PD-1 is expressed by T cells and prevents them from killing cancer cells. When PH-762 reduces PD-1 expression, the "brakes" on the immune system are released and T cells are activated to kill the cancer cells. PH-762 is being developed as a standalone drug therapy with local intratumoral administration. In addition, it is also being developed as a critical component of cellular immunotherapy, more specifically, to improve tumor cell killing capability of adoptively transferred tumor infiltrating lymphocyte (TIL) therapy.

AboutPhio Pharmaceuticals Corp.

Phio Pharmaceuticals Corp. (Nasdaq: PHIO) is a clinical stage biotechnology company developing the next generation of immuno-oncology therapeutics based on its self-delivering RNAi (INTASYL) therapeutic platform. The Company's efforts are focused on silencing tumor-induced suppression of the immune system through its proprietary INTASYL platform with utility in immune cells and the tumor microenvironment. The Company's goal is to develop powerful INTASYL therapeutic compounds that can weaponize immune effector cells to overcome tumor immune escape, thereby providing patients a powerful new treatment option that goes beyond current treatment modalities. For additional information, visit the Company's website, http://www.phiopharma.com.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as "intends," "believes," "anticipates," "indicates," "plans," "expects," "suggests," "may," "would," "should," "potential," "designed to," "will," "ongoing," "estimate," "forecast," "target," "predict," "could" and similar references, although not all forward-looking statements contain these words. Forward-looking statements are neither historical facts nor assurances of future performance. These statements are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements as a result of a number of important factors, including, but not limited to, the impact to our business and operations by the ongoing coronavirus pandemic, the development of our product candidates, results from our preclinical and clinical activities, our ability to execute on business strategies, our ability to develop our product candidates with collaboration partners, and the success of any such collaborations, the timeline and duration for advancing our product candidates into clinical development, the timing or likelihood of regulatory filings and approvals, the success of our efforts to commercialize our product candidates if approved, our ability to manufacture and supply our product candidates for clinical activities, and for commercial use if approved, the scope of protection we are able to establish and maintain for intellectual property rights covering our technology platform, our ability to obtain future financing, market and other conditions and those identified in our Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q under the caption "Risk Factors" and in other filings the Company periodically makes with the SEC. Readers are urged to review these risk factors and to not act in reliance on any forward-looking statements, as actual results may differ from those contemplated by our forward-looking statements. Phio does not undertake to update forward-looking statements to reflect a change in its views, events or circumstances that occur after the date of this release, except as required by law.

Contact Phio Pharmaceuticals Corp.[emailprotected]

Investor ContactAshley R. RobinsonLifeSci Advisors[emailprotected]

SOURCE Phio Pharmaceuticals Corp.

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Phio Pharmaceuticals Announces Preclinical Data Demonstrating PH-762 Enhances Persistence of T cells for Tumor Cell Killing as Presented by Helmholtz...

The three major types of blood cancer are leukemia, lymphoma, and myeloma. All three types usually affect the growth and function of white blood cells. Leukemia affects immature white blood cells, lymphoma affects lymphocytes, and myeloma affects plasma cells.

This information is from the American Society of Hematology.

These are the most common types of blood cancer, but there are also rare types that affect other kinds of blood cells, or that affect structures within the blood system, such as the spleen.

Keep reading to learn more about the different types of blood cancer.

There are three main types of blood cancer. They are:

Blood cancers affect how blood cells grow and die. They typically cause a specific type of blood cell to grow abnormally, meaning they do not function as they should. For example, they may not provide protection against infections, or fail to clot when a person is bleeding.

In most cases, the cancer starts in the bone marrow, which is where the body makes new blood cells. Cancerous blood cells can live longer than healthy cells, meaning they crowd out the remaining healthy blood cells in the bone marrow and impair their production.

Below is more information on each type of blood cancer.

Leukemia is a cancer of the white blood cells that exist in bone marrow.

Bone marrow is responsible for making new blood cells. This process begins with stem cells, which have the potential to become a range of different types of blood cells.

Typically, these cells go through a cycle of maturation, multiplication, and death. In leukemia, though, young white blood cells do not mature as they should. They remain immature, functioning less well but multiplying and surviving better than healthy cells in the bone marrow.

Doctors classify cases of leukemia based on whether they are acute or chronic, and whether they begin in myeloid or lymphoid cells.

Acute types are fast growing, while chronic types are slow growing. Myeloid and lymphoid cells are different types of stem cells.

The broad subtypes include:

Leukemia most often affects adults, but among the cancers children and teenagers experience, it is the most common. In total, leukemia accounts for nearly 1 in 3 of all cancers in these age groups.

Lymphoma is a cancer that affects lymphocytes, which are a type of white blood cell that fight infections.

These cells circulate around the body via the lymphatic system, which is a network of vessels and tubes that transports a fluid known as lymph.

When lymphocytes change into lymphoma cells, they multiply and collect in lymph nodes and other tissues. Since healthy lymphocytes fight infections, this cancer impairs a persons immunity over time. The main subtypes are Hodgkin and non-Hodgkin lymphoma.

This type of lymphoma begins when cancerous lymphocytes multiply and crowd out healthy ones. As the cells multiply, they form masses, typically in the lymph nodes.

This usually forms in the lymph nodes and lymphatic tissue in organs, such as the skin or stomach. In some people, it also affects the bone marrow and blood. Non-Hodgkin lymphoma may involve one site or many sites within the body. It has many subtypes.

Myeloma affects plasma cells, which are a type of white blood cell that make antibodies. Antibodies are proteins that help defend the body from infections.

Similarly to leukemia, myeloma also begins in the bone marrow. The cancerous plasma cells multiply so much that they crowd out healthy bone marrow cells, impairing the bodys ability to make all kinds of blood cells.

The main subtypes are multiple myeloma and plasmacytoma. Multiple myeloma is the most common, and affects multiple sites in the body.

Plasmacytoma often occurs in the bones, muscles, skin, or lungs. Doctors refer to a single tumor as solitary plasmacytoma. They call tumors that occur outside of the bones extramedullary plasmacytoma.

Some rarer types of blood cancer include:

There are also several rare subtypes of lymphoma, such as:

The three main types of blood cancer are leukemia, lymphoma, and myeloma. Leukemia starts in the bone marrow and usually affects immature white blood cells. Lymphoma affects lymphocytes, while myelomas affect plasma cells.

Since all three types affect cells that fight infections, these blood cancers can impair immunity. There are also cancers that affect other types of blood cells, such as red blood cells and platelets.

Continued here:
Types of blood cancer: Leukemia, lymphoma, and more - Medical News Today

Scientists from the University of Bristol and NHS Blood & Transplant (NHSBT) have discovered a rare new blood group system. The findings, published in Blood, the journal of the American Society of Hematology, also solve a 30-year mystery.

A persons blood type is determined by the presence or absence of proteins known as blood groups that are present on the surface of red blood cells. Although most people are familiar with the concept of blood groups such as ABO or Rh (the plus or minus), there are many other important blood groups. Where mismatch exists between one persons blood and that of another, the possibility of alloimmunisation (the process by which a person generates an antibody against a blood group antigen that they do not carry) arises. The presence of alloantibodies can have clinical consequences in transfusion or pregnancy by triggering an attack by the immune system

Researchers from Bristols School of Biochemstry and NHSBTs International Blood Group Reference Laboratory (IBGRL) spearheaded an international collaboration which sought to investigate a 30-year mystery surrounding the basis of three known, but genetically uncharacterised, antigens that did not fit into any known blood group system.

In this study, individuals with alloantibodies against a collection of antigens termed Er, that were first observed more than 30-years ago, were investigated by applying a powerful technique allowing simultaneous analysis of all their gene coding DNA sequences. Specific changes were identified in the gene coding for the Piezo1 protein, which would result in the production of an altered protein on the cell surface of these individuals. Using gene editing in an immortalised cell-line developed in Bristol, the Piezo1 protein was first removed and then reintroduced to definitively prove that alloantibodies to Er antigens (including two never before reported) bind to Piezo1, and that Piezo1 is required for Er antigen expression.

Using a combination of cutting-edge DNA sequencing and gene-editing techniques, the team were able to conclusively show that Piezo1, a protein of widespread biological interest, is the carrier for these sites (and more) and, in so doing, establish Er as a new blood group system.

Sadly, alloantibodies found in two pregnant women to two newly discovered Er antigens reported in this work were associated with tragic loss of their babies. Discovering the genetic basis of blood groups allows scientists to develop new tests to identify those with uncommon blood groups, with the aim of providing the best possible care for patients with even the rarest of blood types. Piezo1 is known to have important roles in both health and disease and, although there is still much for us to understand, the teams breakthrough further enhances our knowledge and represents another new milestone in blood sciences.

Dr Tim Satchwell, one of the studys lead authors at the University of Bristol, said: This study is a great example of how new technologies can combine with more traditional approaches to address long-standing questions that would have been impossible to answer not that many years ago. The fact that Er turned out to be Piezo1, a protein with such widespread interest makes it even more intriguing.

Professor Ash Toye, Professor of Cell Biology at the University of Bristol and Director of the NIHR Blood and Transplant Research Unit, said: This work demonstrates that even after all the research conducted to date, the simple red blood cell can still surprise us. Piezo proteins are mechanosensory proteins that are used by the red cell to sense when its being squeezed. The protein is present at only a few hundred copies in the membrane of each cell. This study really highlights the potential antigenicity of even very lowly expressed proteins and their relevance for transfusion medicine.

About NHS Blood and Transplant

NHS Blood and Transplant is a joint England and Wales Special Health Authority. We provide the blood and plasma donation service for England and the organ donation service for the UK. We also provide donated tissues, stem cells, and cord blood. NHSBT delivers specialist services to hospitals and carries out world leading research. We are an essential part of the NHS, saving and improving lives through public donation.

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September: er-blood | News and features - University of Bristol

You probably know what hormones are, and you may have at least heard about stem cells, but what is a growth factor? According to Britannica, it is a protein that stimulates growth in specific tissues. There are many types of growth factors, each with the job of repairing certain body parts. Some growth factors include epidermal growth factor (responsible for skin repair), platelet-derived growth factor (responsible for repairing muscles and connective tissues), and nerve growth factor (responsible for stimulating brain cell growth and repair).

According to a 2020 mini-review in Frontiers in Bioengineering and Biotechnology, growth factors are critical for tissue repair and regeneration. In short, growth factors help maintain skin health and heal wounds. As you age and fewer growth factors are available to help with repair and regeneration, injuries take longer to heal. Stem cells factor in because they release growth factors to instigate wound healing, according to a 2010 study in theInternational Journal of Stem Cells.

And the sex hormones estrogen and testosterone play a part in wound healing too. Low estrogen levels or high amounts of testosterone can slow healing. For women, estrogen levels drop after menopause, resulting in slowed healing time (via Wounds).

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Here Is Why You Heal Slower As You Age - Health Digest

Visiongain Reports Ltd

Visiongain has published a new report entitled the Single Cell Analysis 2022-2032. It includes profiles of Single Cell Analysis and Forecasts Market Segment by Type (Consumables, Instruments) Market Segment by Application, (Cancer, Immunology, Neurology, Stem Cell, Non-invasive Prenatal Diagnosis, In-vitro Fertilization, Others) Market Segment by Technique, (Flow Cytometry, Next Generation Sequencing, Polymerase Chain Reaction (PCR), Microscopy, Mass Spectrometry, Other Techniques) Market Segment by Cell Type, (Human Cells, Animal Cells, Microbial Cells) Market Segment by End Use, (Academic & Research Laboratories, Biotechnology and Pharmaceutical Companies, Hospitals and Diagnostic Laboratories, Others) PLUS COVID-19 Impact Analysis and Recovery Pattern Analysis (V-shaped, W-shaped, U-shaped, L-shaped) Profiles of Leading Companies, Region and Country.

The global single cell analysis market was valued at US$3,255.0 million in 2022 and is projected to grow at a CAGR of 15.1% during the forecast period 2022-2032.

Integration of Microfluidics in Single-Cell AnalysisSingle-cell analyses of various types are increasingly widely employed to solve a wide range of biological problems, and as their popularity grows, potential downsides to these methods become more evident. Workflows can be time-consuming, low-throughput, and prone to contamination, depending on the application.

Microfluidic designs have been widely used to enhance single-cell workflows in all major stages of single-cell applications, right from cell sorting to lysis, sample processing, and readout, owing to their advantages of high throughput, low reaction volume, and compatibility with bio-inert materials. However, creating an integrated microfluidic device that covers the complete single-cell operation from start to end remains difficult in the global market. In biology and chemistry, microfluidics has known to be a great tool for analysis of single cells in various end uses.

Story continues

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Single-Cell Analysis Market Report 2022-2032

How this Report Will Benefit You?Visiongains 570 page report provides 389 tables and 399 charts/graphs. Our new study is suitable for anyone requiring commercial, in-depth analyses for the global single cell analysis market, along with detailed segment analysis in the market. Our new study will help you evaluate the overall global and regional market for single cell analysis. Get the financial analysis of the overall market and different segments including type, application, technique, cell type, end use and capture higher market share. We believe that high opportunity remains in this fast-growing single cell analysis market. See how to use the existing and upcoming opportunities in this market to gain revenue benefits in the near future. Moreover, the report would help you to improve your strategic decision-making, allowing you to frame growth strategies, reinforce the analysis of other market players, and maximise the productivity of the company.

What are the Current Market Drivers?

Technological Advancements in Single-Cell Analysis ProductsThe advancement in the single cell amplification and manipulation techniques has resulted in the utilization of high output technologies in assays, resulting in augmented revenue. The implementation of single cell genomic or transcriptomic process for analysis in biomedical research has also increased due to the quick expansion of microfluidic equipment. Also, due to the technological innovations in sequencing techniques, the landscape of single-cell omics research, comprising transcriptomic, genomics, and epigenomics is changing. The ability to process a maximum number of samples has been assisted by substantial developments in sequencing repeatability together with reducing prices.

Growth in Stem Cell ResearchWith their self-renewal and plan potent differentiation potential, stem cells show great promise for therapeutic applications to some refractory diseases. such as myocardial infarction, stroke, and diabetes Owing to the heterogeneity of single cells, gene expression is highly diverse between cells even within a single tissue, making precise identification and analysis of biological properties difficult This hinders their further research and applications. However, single-cell analysis assists in characterizing and analyzing stem cells.

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Single-Cell Analysis Market Report 2022-2032

Where are the Market Opportunities?

High Growth Potential of Single-Cell SequencingRising growth of sequencing of individual cells is likely to exhibit huge potential opportunity for the market growth. It is a valuable technology for the identification of biomarkers, which are used to diagnose and track the onset and progression of a disease, as well as the patient's response to treatment. Companies are working on producing instruments and reagents that are suitable for single-cell sequencers since SCS technology delivers extensive details about genetic alterations.

Several sophisticated SCS instruments are projected to be developed and launched in the market in the future years, owing to the significant growth potential of this area.

Emergence of Asia Pacific Market

Rising investment in biology research across the global market along with the rising emphasis of key market players to expand their footprint in lucrative Asia Pacific region are the major factors propelling the market growth. Various economies in the region such as India, Japan, South Korea, and Southeast Asia in the region is anticipated to become driving force for expansion of single cell analysis market over the forecast period.

Several market players are investing in the development of cell based research facilities in emerging Asian countries. primarily due to the increasing prevalence of chronic diseases, improvements in infrastructural facilities for research, and favourable legislation for cell-based research. For instance, in June 2018, Agilent opened its new logistics hub in Shanghai to enable the faster delivery of supplies, consumables, and parts to laboratories in China.

Competitive LandscapeThe major players operating in the Single Cell Analysis market are Agilent Technologies, Inc., Beckman Coulter Inc., Becton, Dickinson and Company, Bio-Rad Laboratories Inc., Fluidigm Corporation, GE Healthcare, Illumina Inc., Merck KGaA, Qiagen NV, Thermo Fisher Scientific, Inc., Promega Corporation, Cytek Biosciences, Tecan Group Ltd., Sartorius AG, and Luminex Corporation. These major players operating in this market have adopted various strategies comprising M&A, investment in R&D, collaborations, partnerships, regional business expansion, and new product launch.

Recent Developments

2nd March 2021, Agilent entered into a definitive agreement to acquire Resolution Bioscience Inc. The acquisition helped to expand Agilents capabilities in NGS-based cancer diagnostics and provide with innovative technology to further accommodate the needs of the fast-growing precision medicine industry.

7th February 2021, Beckman Coulter Life Sciences Partners with Fry Laboratories and BioID Genomics on Next Generation DNA Sequencing

Avoid missing out by staying informed order our report now.

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Do you have any custom requirements we can help you with? Any need for a specific country, geo region, market segment or specific company information? Contact us today, we can discuss your needs and see how we can help: dev.visavadia@visiongain.com

About Visiongain

Visiongain is one of the fastest-growing and most innovative independent market intelligence around, the company publishes hundreds of market research reports which it adds to its extensive portfolio each year. These reports offer in-depth analysis across 18 industries worldwide. The reports cover a 10 year forecasts, are hundreds of pages long, with in depth market analysis and valuable competitive intelligence data. Visiongain works across a range of vertical markets, which currently can influence one another, these markets include automotive, aviation, chemicals, cyber, defence, energy, food & drink, materials, packaging, pharmaceutical and utilities sectors. Our customized and syndicatedmarket research reportsmean that you can have a bespoke piece of market intelligence customized to your very own business needs.

Contact:Dev VisavadiaPR at Visiongain Reports LimitedTel: + 44 0207 336 6100Email: dev.visavadia@visiongain.com

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Global Single Cell Analysis Market is Projected to Grow at a CAGR of 15.1% By 2032: Visiongain Reports Ltd - Yahoo Finance UK

image:Brett Teubner Ph.D., Mary Patton Ph.D. and Christopher Davenport Ph.D., St. Jude Department of Developmental Neurobiology. view more

Credit: St. Jude Children's Research Hospital

Williams-Beuren syndrome (WBS) is a rare disorder that causes neurocognitive and developmental deficits. However, musical and auditory abilities are preserved or even enhanced in WBS patients. Scientists at St. Jude Childrens Research Hospital have identified the mechanism responsible for this ability in models of the disease. The findings were published today in Cell.

Understanding what causes the superior auditory ability in WBS patients may provide a target for treating the disease in addition to helping advance research on the ability to discriminate between sounds. WBS offers insight into the mechanisms that underlie enhanced auditory abilities. For instance, some people with WBS have perfect pitch, which is the ability to differentiate between notes or frequencies without a reference guide.

WBS stands out among neurodevelopmental disorders because children with the disorder, despite profound learning disabilities, can have a higher prevalence of superior musical and linguistic abilities than children in the general population, said corresponding author Stanislav Zakharenko, M.D., Ph.D., St. Jude Department of Developmental Neurobiology. We were fascinated by that and wanted to know more about how a disorder that is caused by a loss of 27 genes could help individuals gain a better than normal ability for auditory processing.

Excited neurons in the auditory cortex

Mouse models of WBS have an enhanced ability to discriminate between sound frequencies. These mice also have improved frequency coding in the auditory cortex, the part of the brain that processes sound. The researchers showed that the enhanced ability to discriminate between frequencies is caused by hyperexcitable interneurons in the auditory cortex.

To understand the cellular biology that underlies enhanced auditory abilities in WBS patients, the researchers conducted an RNAseq experiment. The data led the researchers to a neuropeptide receptor called VIPR1, which is reduced in the auditory cortex of individuals with WBS. The reduction in VIPR1 was also found in cerebral organoids, advanced models made in the laboratory using human induced pluripotent stem cells.

The scientists found that the transcription factor Gtf2ird1, encoded by one of the 27 genes lost in those with WBS, regulates VIPR1. Deleting or overexpressing VIPR1 in the auditory cortex can mimic or reverse the auditory effects seen in WBS. Thus, it is Gtf2ird1 downregulating VIPR1 that is responsible for the impact of WBS on auditory ability.

I didnt know a lot about VIPR1 before it popped up in our data because the role of this family of receptors in the brain is under-appreciated compared to other neuromodulator or neurotransmitter receptors, said first-author Christopher Davenport, St. Jude Department of Developmental Neurobiology. Our findings show that they can strongly impact information processing and behavior and are likely relevant for other behaviors and diseases as well.

This work suggests that reducing neuronal hyperexcitability might be a general mechanism for treating WBS through targeting VIPR1, Zakharenko said. It also opens up new directions to learn about musicality and how our brain differentiates sounds based on these findings in models of WBS.

Authors and funding

The studys other authors are Brett Teubner, Seung Baek Han, Mary Patton, Tae-Yeon Eom, Dusan Garic, Benjamin Lansdell, Abbas Shirinifard, Ti-Cheng Chang, Jonathon Klein, Shondra Pruett-Miller and Jay Blundon all of St. Jude.

The study was supported by grants from the National Institutes of Health (R01MH097742, R01DC012833), the Stanford Maternal and Child Health Research Institute Uytengsu-Hamilton 22q11 Neuropsychiatry Research Program and ALSAC, the fundraising and awareness organization of St. Jude.

St. JudeChildren's Research Hospital

St. JudeChildren's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed atSt. Judehave helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened 60 years ago.St. Judefreely shares the breakthroughs it makes, and every child saved atSt. Judemeans doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill fromSt. Judefor treatment, travel, housing and food so families can focus on helping their child live. To learn more, visitstjude.orgorfollowSt. Judeon social media at@stjuderesearch.

Experimental study

Animals

Innate frequency-discrimination hyperacuity in Williams-Beuren syndrome mice

23-Sep-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Findings explain exceptional auditory abilities in Williams-Beuren Syndrome - EurekAlert