Category Archives: Cell Therapy

HOUSTON, Sept. 21, 2022 (GLOBE NEWSWIRE) -- Alaunos Therapeutics, Inc. (Alaunos or the Company) (Nasdaq: TCRT), a clinical-stage oncology-focused cell therapy company, today announced early clinical data from the first patient in its ongoing TCR-T Library Phase 1/2 trial. The data will be presented during a proffered talk at the CRI-ENCI-AACR Sixth International Cancer Immunotherapy Conference (CICON) being held in New York, NY from September 28 through October 1, 2022.

The encouraging data from the first patient in our trial highlight the potential of our non-viral TCR-T cell therapies to treat solid tumors even at the lowest doses in the study design, said Kevin S. Boyle, Sr., Chief Executive Officer of Alaunos. Patients with solid tumors represents a large unmet medical need, and the results from the first patient are quite promising that our TCR-T cell therapy may offer them hope. We look forward to treating additional patients and are grateful for the continued support from our investigators, patients and our dedicated team.

Marcelo V. Negrao, MD, Department of Thoracic/Head & Neck Med Onc, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center added, These clinical data, where a greater than 51% tumor regression in a patient with NSCLC was observed, are encouraging. We believe this data adds to the growing body of evidence indicating that targeting shared tumor-specific hotspot mutations using TCRs has the potential to transform the way we treat solid tumor cancers. In addition, we believe that the manageable safety and tolerability profile is reassuring, and we look forward to continuing enrollment in the study.

The TCR-T Library Phase 1/2 trial is an open label, dose escalation study being conducted at MD Anderson. The trial is enrolling patients with non-small cell lung, colorectal, endometrial, pancreatic, ovarian, and bile duct cancers that have a matching human leukocyte antigen (HLA) and hotspot mutation pairing in Alaunos TCR-T library.

Key highlights to be presented:

Details of the presentation are as follows:

Title: Objective clinical response by KRAS mutation-specific TCR-T cell therapy in previously treated advanced non-small cell lung cancerPresenter: Marcelo V. Negrao, MD, Department of Thoracic-Head & Neck Medical Oncology, Division of Cancer Medicine at MD AndersonDate and Time: Friday, September 30, 2022, 9:00-9:15am ETSession Title: Session 6: Cellular Therapies: Engineering T cells

The full abstract may be accessed by visiting http://www.cancerimmunotherapyconference.org.

About Alaunos TherapeuticsAlaunos is a clinical-stage oncology-focused cell therapy company, focused on developing T-cell receptor (TCR) therapies based on its proprietary, non-viral Sleeping Beauty gene transfer technology and its TCR library targeting shared tumor-specific hotspot mutations in key oncogenic genes including KRAS, TP53 and EGFR. The Company has a clinical and strategic collaboration with the National Cancer Institute. For more information, please visit http://www.alaunos.com.

Forward-Looking Statements Disclaimer This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as may, will, could, expects, plans, anticipates, believes or other words or terms of similar meaning. These statements include, but are not limited to, statements regarding the Company's business and strategic plans, the anticipated outcome of preclinical and clinical studies by the Company or its third-party collaborators, the Companys manufacturing capabilities and the timing of the Company's research and development programs, including the expected timeline for enrolling and dosing patients and the timing and forums for announcing data from the Company's clinical trials. Although the management team of Alaunos believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Alaunos, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include, among other things, changes in the Companys operating plans that may impact its cash expenditures; the uncertainties inherent in research and development, future clinical data and analysis, including whether any of Alaunos product candidates will advance further in the preclinical research or clinical trial process, including receiving clearance from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies to conduct clinical trials and whether and when, if at all, they will receive final approval from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies and for which indication; the strength and enforceability of Alaunos intellectual property rights; and competition from other pharmaceutical and biotechnology companies as well as risk factors discussed or identified in the public filings with the Securities and Exchange Commission made by Alaunos, including those risks and uncertainties listed in the most recent periodic report filed by Alaunos with the Securities and Exchange Commission. Alaunos is providing this information as of the date of this press release, and Alaunos does not undertake any obligation to update or revise the information contained in this press release whether as a result of new information, future events, or any other reason.

Investor Relations Contact:Alex LoboStern Investor Relationsalex.lobo@sternir.com

1 Cyclophosphamide (60 mg/kg for 2 days) and Fludarabine (25 mg/m2 for 5 days)

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Alaunos Therapeutics Highlights Data from TCR-T Library Phase 1/2 Trial at the CRI-ENCI-AACR Sixth International Cancer Immunotherapy Conference -...

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The concept of therapeutic cancer vaccines emerged in the late 1980s but, some 35 years later, it still hasnt resulted in an approved product. The advances in immuno-oncology and adaptive cell therapy that began about a decade ago, however, are enabling fresh, biology-driven approaches with the potential to bring therapeutic cancer vaccines much closer to fruition.

One challenge has been the question of how to elicit an immune response to a tumor, which is a mutated part of the self rather than a foreign entity.

Another problem is that tumors from different sites in the body have different mutations, said Muhammad Al-Hajj, Ph.D., CSO at IO Biotech in an interview with BioSpace. So, while a specific cancer vaccine might work against one tumor, it wont wipe out all the tumor cells throughout the body.

A third hurdle is that tumors protect themselves with a shield of normal cells. For example, Al-Hajj said, In breast cancer, the percentage of actual tumor cells within the mass is less than 50 percent. In pancreatic tumors, 90 percent of the cells are non-cancerous. Thats why pancreatic cancer is so difficult to treat. It brings a whole network of normal cells, that help protect the cancerous cells from the immune system. Therefore, You need something that could wipe out most or all of the cancer cells, he explained.

Boosting the Potential of Immuno-oncology

Checkpoint inhibitors, a leading immuno-oncology strategy, arent effective for all patients. They also have multiple toxicities when combined with other agents.

IO Biotech has a technology platform, called T-win, that activates T cells to directly kill immunosuppressive cells and gently modulate the tumor microenvironment to be less receptive to tumors. Its lead candidate, IO102/IO103, targets the indoleamine 2,3-dioxygenase (IDO) enzyme and programmed death ligand 1 (PD-L1).

Whats particularly novel is that rather than just targeting the cancer cells within the tumor, IO Biotech is developing a vaccine against the key elements within the tumor that pushes the T cells away.

Vaccination modulates the environment in a way that is very gentle and non-toxic, Al-Hajj said. This is not a standard vaccine. Its a vaccine for tumor microenvironment targets. The idea is to modulate the tumor microenvironment and to combine (the vaccine) with a very powerful immune therapylike a checkpoint inhibitorto allow them to infiltrate better.

A Phase I/II trial of 30 melanoma patients showed that vaccination elicited a response in about 80 percent of the patients, whereas a checkpoint inhibitor elicited a response in slightly less than 50 percent.

Biomarker analysis proved the cells start to infiltrate the tumor. Now we are working to prove it in a much larger trial, Al-Hajj shared. Additional clinical trials are underway in first-line solid tumors and as a neo-adjuvant/adjuvant for solid tumors for lung, head & neck and bladder cancers. The vaccine holds FDA breakthrough designation.

There are, of course, many different approaches to therapeutic cancer vaccines.

Targeting the Lymph Nodes

Elicio Therapeutics is targeting the lymph nodes - which the company calls the brain center of the immune system - with its Amphiphile (AMP) platform.

The role the lymph nodes play in organizing the immune response has been known for a very long time, said Pete DeMuth, Ph.D., CSO at Elicio. But, I think we just assumed that after injection, everything sort of went there eventually so it didnt need a lot of intentional design consideration.

Over time, though, scientists discovered there actually were very large differences in the way injected agents distribute throughout the body, DeMuth told BioSpace. Now were starting to see an emphasis on lymph node targeting because we understand enough about the underlying biology to design technologies that allow us to optimize lymph node delivery.

One of the first challenges in this approach is to design molecules of the optimal size to reach the lymph nodes.

Molecules that are too large or too small wont get there very well, DeMuth said. Then, once the molecules arrive, they must be delivered to the right cells within the lymph nodes.

So, Elicio founder and MIT professor Darrell Irvine, Ph.D., designed AMP to direct drugs or other payloads to the lymph nodes. His approach leveraged engineering, material science and biology.

We modify a vaccine molecule by linking a lipid to it to teach the immune system how to collect it and use it as information to develop a response that will protect against cancer, DeMuth explained. The lipid allows the vaccine to bind to albumin (a protein in the tissue), which acts as a shuttle bus to transport things from the tissue into the lymph nodes. The AMP is like the bus pass that allows these agents to get on the shuttle bus.

This system can be applied to many different vaccine or drug agents, including possibly drugs that were limited in their activity because they couldnt reach the immune cells or because they went to other places in the body and caused toxicities, he suggested.

By giving them this AMP modification, (they go) straight into the lymph nodes where they can modulate the biology of the immune cells and simultaneously reduce their exposure to other sites in the body that might drive safety concerns or have toxicities that would limit their usefulness.

The AMP system is currently undergoing a Phase I trial to treat mutant KRAS-driven cancers in the gastrointestinal tract or lungs. Early results havent been released, but DeMuth says he is very optimistic given our preclinical results and the history around this type of therapy.

Going After Cancer Cells Survival Mechanism

In another advance, IMV Inc. recently announced positive data in metastatic bladder cancer patients using its cancer vaccine, Maveropepimut-S (MVP-S) also known as DPX-Survivac.

It shows complete responses, even in patients who had already progressed through immune checkpoint inhibitors. Response are beyond 600 or 700 days and are still ongoing, said Jeremy Graff, Ph.D., CSO, in an interview with BioSpace.

What makes MVP-S unique among cancer vaccines is that its designed to instigate an immune response to a very common cancer protein called survivin, Graff said. Survivin is a protein that many cancers up-regulate during progression. As the name implies, it actually enables the survival of cancer cells.

What distinguishes MVP-S from prior cancer vaccines, Graff explained, is that we not only put the information into our therapeutic to provide a specific survivin signal, but we also put information to instigate the functionality of antigen-presenting cells (APCs) as well as CD4 T cells. This approach encapsulates multiple pieces of instruction that drive an immune response.

The duration of response for survivin-specific T cell activation exceeds two years. Duration is particularly important. CAR T cells often dont persist even though we put billions of cells into patients, Graff noted.

Data released from a Phase IIa study in summer 2021 showed durable responses among ovarian cancer patients that extended progression-free survival to about 20 months in nearly half the patients (who had already been exposed to multiple chemotherapies) who were treated with MVP-S. This was compared to about 10 to 12 months for those treated with chemotherapy.

A new trial has been submitted to the FDA and Health Canada to assess the clinical benefit for MVP-S and low-dose intermittent cyclophosphamide in platinum-resistant ovarian cancer patients.

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Cancer Vaccines Push Toward Viability with New Approaches and Targets - BioSpace

SAN DIEGO & SINGAPORE--(BUSINESS WIRE)--ImmunoScape, a pre-clinical biotechnology company focused on the discovery and development of next-generation TCR-T-cell therapeutics today announced that it has raised $14M in new financing. Existing investor Anzu Partners led the round with participation from new investor Amgen Ventures and Singapore-based global investor EDBI.

ImmunoScapes differentiated Deep Immunomics platform utilizes the companys proprietary combinatorial barcoding technology to enable the discovery and in-depth characterization of rare cancer-specific T-cells at high resolution. ImmunoScapes platform is able to simultaneously evaluate tens of millions of T-cells in blood samples from hundreds of cancer patients to identify rare clinically relevant T-cell clones. The corresponding TCRs are then evaluated and prioritized to build a diverse portfolio of TCR-T-cell therapies.

By leveraging computational biology and machine learning, together with high throughput screening and evaluation of T-cell clones, ImmunoScape is able to efficiently identify novel T-cell therapy targets and TCR candidates. ImmunoScape has extensively validated its computational platform using virus-specific T-cells and is applying the same methods to build an extensive portfolio of cancer-specific TCRs.

We have made significant strides in our discovery program and have identified several compelling clinical TCR candidates using our Deep Immunomics platform, said Choon Peng Ng, CEO, ImmunoScape. The new funding will allow us to expedite our development efforts and help us to advance our therapeutic candidates toward the clinic. We are especially delighted that Amgen Ventures has become an investor and we look forward to working with their team to address important unmet medical needs with ImmunoScapes technology.

Amgen invests in promising new solutions to address healthcares biggest challenges, especially those that offer unique, value-based approaches that align with our mission to serve patients fighting serious illness, said Philip Tagari, vice president of research (therapeutic discovery), Amgen. ImmunoScapes Deep Immunomics and machine learning platforms have the potential to help uncover new treatments as we continue to develop the next generation of innovative medicines. We are excited to work with their team to unlock the full power of this technology.

With research laboratories in both San Diego and Singapore, ImmunoScape is one of the global pioneers of TCR discovery. Their unique high-throughput TCR discovery and evaluation platform has an unprecedented capacity to test millions of human T-cells against hundreds of cancer antigens, said David Michael, managing partner at Anzu Partners. From their origins at Singapores Agency for Science, Technology, and Research (A*Star), the companys global team of immunologists are pursuing major breakthroughs in TCR cell therapy. We are delighted to work more closely with Amgen on these important efforts.

To learn more about ImmunoScape, please visit https://immunoscape.com/.

About ImmunoScapeImmunoScape is a pre-clinical biotechnology company focused on the discovery and development of next-generation TCR cell therapies in the field of oncology. The company's proprietary Deep Immunomics technology and machine learning platforms enable highly sensitive, large-scale mining and immune profiling of T cells in cancer patient samples to identify novel, therapeutically relevant TCRs across multiple types of solid tumors. ImmunoScape has multiple discovery programs ongoing and will be progressing towards IND-enabling studies and entry into the clinic. For more information, please visit https://immunoscape.com/.

About Anzu PartnersAnzu Partners is an investment firm that focuses on industrial and life science technology companies with the potential to transform their industries. Anzu works with entrepreneurs to develop and commercialize technological innovations by providing capital alongside deep expertise in business development, market positioning, intellectual property, global connectivity, and operations. For more information, please visit https://anzupartners.com/.

About Amgen VenturesAmgen Ventures is Amgen's corporate venture capital fund, dedicated to investing in emerging companies and technologies to advance promising new medicines and solutions to healthcares biggest challenges. For more information, please visit https://amgenbd.com

About EDBIInvesting since 1991, EDBI is a Singapore-based global investor in select high growth technology sectors ranging from Information & Communication Technology (ICT), Emerging Technology (ET), Healthcare (HC) and promising Singapore SMEs in strategic industries. As a value creating investor, EDBI assists companies achieve their ambitious goals by leveraging our broad network, resources, and expertise. With our growth capital, EDBI supports companies seeking to expand in Asia and globally through Singapore. For more information, please visit https://www.edbi.com.

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ImmunoScape Raises $14M to Facilitate the Discovery and Characterization of Cancer-Specific T-cell Receptors - Business Wire

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Prescient Therapeutics (PTX) has unveiled a novel adjuvant for enhancing cellular immunotherapy.

The CellPryme-A product was designed to be administered to cancer patients as an intravenous infusion in combination with cellular immunotherapy, such as PTXs CAR-T cell therapy. This is used to address the hostile tumour microenvironment that cellular immunotherapies face.

CellPryme-A can be administered either before or alongside cellular immunotherapy.

Prescient said in animal models, CellPryme-A had been shown to reduce the number of suppressive regulatory T cells surrounding solid tumours that counteracted the effectiveness of CAR-T and other cancer therapies.

While CellPrymeA demonstrated superior tumour killing and host survival in pre-clinical studies, its effects were even greater when used together with Prescients CAR-T manufacturing technology, CellPryme-M.

The company presented this new data at the seventh annual CAR-TCR Summit in Boston.

Prescient Managing Director and CEO Steven Yatomi-Clarke said the company was delighted to finally unveil CellPryme-A as a distinct but complementary addition to CellPryme-M.

Together with Prescients next-generation CAR platform, OmniCAR, Prescient has placed itself enviably at the forefront of cellular immunotherapy by creating technologies that overcome the challenges facing the field, Mr Yatomi-Clarke said.

The company said CellPryme-Awas now ready for clinical testing and could be incorporated into clinical studies of existing cell therapies.

Prescient Therapeutics was down 1.35 per cent and trading at 18 cents at 1:29 pm AEST.

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Prescient Therapeutics (ASX:PTX) unveils new treatment to boost CAR-T performance - The Market Herald

Nizar Tannir, MD: Thank you, Scott, for sharing with us the data from the CLEAR study. I wanted to take this opportunity to ask Moshe [a question]. Moshe, youre familiar with the data, and you saw the data on the slides that Scott presented. In your mind, whats the rationale of combining lenvatinib with pembrolizumab? Is this impressive? The CR [complete response] rate was 16%, OR [overall response] was 71%, median PFS [progression-free survival] was 23.9 months, with a PFS hazard ratio of 0.39 and the OS [overall survival] benefit. Is that because lenvatinib is a potent VEGFR TKI [tyrosine kinase inhibitor]? Or do you think the fact that it also inhibits BFGF plays a role and produces these impressive results? Whats your take on that?

Moshe Ornstein, MD, MA: That was a great overview of the data. In some ways, were working backward. Of all the I/O [immuno-oncology]TKIs that have been approved, the CLEAR trial with lenvatinib and pembrolizumab was the last piece of the puzzle. That said, despite it being the last piece of the puzzle, it sets the bar and the new benchmark for what wed need to see to change the standard of care for treatment-nave metastatic clear cell RCC [renal cell carcinoma].

Getting to your question as to why those results were so impressive, Im not convinced that any single TKI is necessarily better or stronger based on the specific targets. Because theyre all VEGFR inhibitors, more important perhaps than the individual targets is the dosing. For the population at large, theres the concept of linear pharmacokinetics when it comes to VEGFR TKIs, such that collectively, a higher dose is generally equated with a higher plasma level and a better response. That said, there are some patients with very high doses whose cancers dont respond, and some patients on very low doses who have exceptional anti-tumor responses.

The No. 1 reason why the efficacy in this regimen was so impressivewith the I/OTKIs were looking at that up-front benefit of response rates and PFSis because they started at a high dose of lenvatinib at 20 mg and, as well see when we review the other I/OTKI regimens, there were different doses for the TKI. If you were to ask many kidney cancer specialists 3 or 4 years ago what data they would need to see from an I/OTKI regimen to have it set as a new benchmark, with numbers like a response rate of 70%-plus, a PFS of close to 2 years, and complete response rates of 16%, most would have said that numbers like that would at least make this combination extremely competitive in the growing landscape, if not set it apart as the optimal choice for the patient who can tolerate the toxicities and that dose of TKI.

Ill summarize by saying that these data are extremely impressive. They set a new benchmark for efficacy in the response rate, CR rate, and PFS components. I also think its related more to the dosing than it is to lenvatinibs different targets compared with some of the other TKIs.

Transcript edited for clarity.

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Rationale for Lenvatinib plus Pembrolizumab Therapy in Frontline Setting in Advanced Clear Cell RCC - Targeted Oncology

CAR T-cell therapy products will soon be available in Saudi Arabia, Singapore and Brazil, following the launch of Gilead and Kite Oncologys latest operations.

Commenting on the expansion into KSA, Eslam Khedr, Regional Business Unit Director for Cell Therapy and Oncology, Gilead and Kite Middle East said: Saudi Arabias Vision 2030 is a key reason Kite selected Saudi Arabia as the location of its first Middle East operation. We are establishing a fully functional oncology/cell therapy business unit in line with international best-in-class protocols with the aim of giving those with cancer the chance to be treated and to offer healthcare of an international standard.

Dedicated Gilead and Kite teams will work to qualify leading hospitals to administer CAR T-cell therapy in each of the new countries after local regulatory approvals. Plans are also in place to increase its workforce in these countries this year.

To date, Kite is the only company dedicated exclusively to the research, development, and manufacturing of cell therapy on a global scale. All its functions dedicated to this focus area are vertically integrated under one leadership team for efficient delivery of the highly specialised and complex end-to-end processes needed to support CAR T-cell therapy.

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CAR T-Cell Therapy operations launched in Saudi Arabia - Omnia Health Insights

The manufacturing of cell therapies is highly complex, often depending on skilled manual labor. The Israeli startup Adva Biotechnology aims to use automation, optical sensing and artificial intelligence to remove the manual component from the process.

Cancer cell therapies such as CAR-T immunotherapies have demonstrated enormous potential for treating forms of blood cancer. Currently available therapies involve extracting a cancer patients immune T cells, genetically engineering them in the lab, and returning them to the patient to kill cancer cells.

One of the drawbacks of these therapies is that growing cells in a manufacturing setting is highly complex. This means that the therapies are expensive and largely limited to the wealthiest nations.

According to Noam Bercovich, vice president of development at the Israeli firm Adva Biotechnology, CAR-T cell therapies have been something that most cancer patients are unable to receive.

All the companies manufacturing this therapy use semi-automated solutions, which demand lots of human input in terms of quantity and expertise, Bercovich added.

To bring more automation into the cell therapy manufacturing process, Adva Biotechnology was founded in 2016 by its CEO Ohad Karnieli in Bar-Lev High-Tech Park in Israel. Adva Biotechnology is working on an automated cell culture kit powered by artificial intelligence and optical sensors.

Prior to founding Adva Biotechnology, Karnieli had served as vice president of technology and manufacturing at the cell therapy firm Pluristem Therapeutics, which is now known as Pluri. He also founded the CDMO Atvio Biotechnology, which was acquired by Orgenesis in 2018.

Bercovich was a process engineering manager at Pluristem and had known Karnieli for almost 12 years before ADVA Biotechnology was founded.

We worked together and [Karnieli] left the place, called me and told me about his idea. And I said Id join right away, recalled Bercovich.

In an online presentation, Advas founder and CEO Ohad Karnieli explained that current manufacturers are only able to measure a few parameters in cell cultures on a few occasions.

We dont really know whats happening inside the system or inside our cultures, he stated. We put the cells in the incubator and we have no idea whats happening. We need much more in-process controls.

The equipment, named ADVA X, uses sensors and artificial intelligence to handle the fine adjustments that are often required when growing cells, such as monitoring and tweaking levels of nutrients in the cell culture medium. It consists of a single-use kit that slots into an electronic system. According to Adva Biotechnology, the kit can culture from 10 million to 20 billion cells in the same chamber. In addition, the kit has the ability to grow CAR-T cells, natural killer (NK) cells, exosomes, viruses and more.

At present, ADVA X is available only to early adopters. After a patent dispute with the CDMO giant Lonza, Adva entered a licensing agreement with Lonza in May 2022 to enable the startup to launch its equipment in the U.S. The device will face its first field test manufacturing an advanced therapy for a clinical trial in 2023.

Once its tested in a clinical trial that is when we can look at the device and say, We made it. Its the real thing, said Bercovich.

Adva is part of a wave of startups geared towards bringing automation to the world of advanced therapy manufacturing, such as Ori Biotech and Cytera Cellworks. Bercovich said that Advas fast adoption of optical sensing technology is what helps the company stand out from the crowd.

Automated cell therapy manufacturing technology such as the ADVA X could also enable the advent of decentralized manufacturing. In this scenario, for example, a CAR-T therapy could be produced at the hospital where a cancer patient is staying, rather than being shipped off to a large, expensive central location.

If I can take my manufacturing and bring it to the patient, a lot of the logistics and the huge footprint are basically eliminated, stated Karnieli. We need decentralized manufacturing with centralized control, meaning remote access, alerts and all these different automation properties.

Adva Biotechnology bankrolled its research with a crowdfunding campaign in 2020, and with a seed round in 2021. The company is now in the middle of raising another funding round.

According to Bercovich, while a lot of attention has been paid to the business potential of automation in cell therapy manufacture, Advas also mindful that these advances can lead to more treatments that save lives.

Behind all this, its a potential cancer treatment, said Bercovich. This is something that we speak about every now and then to not forget.

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Adva Biotechnology is using artificial intelligence to manufacture cell therapies - Labiotech.eu

BEIJING & GUANGZHOU, China--(BUSINESS WIRE)--Biocytogen Pharmaceuticals (Beijing) Co., Ltd. ("Biocytogen", HKEX: 02315) announced a strategic collaboration with Guangzhou FineImmune Biotechnology Co., LTD. (FineImmune) to co-develop cell-based therapeutic drugs targeting intracellular tumor-associated antigens. Biocytogen will use its proprietary TCR-mimic antibody platform to discover fully human antibody sequences that will be further developed using FineImmunes unique cell therapy platform.

Biocytogens TCR-mimic antibody development platform utilizes its proprietary fully human antibody RenMiceTM (RenMabTM and RenLite mice) that have been further engineered to express a human leukocyte antigen (HLA) gene. Antibodies against intracellular tumor-associated antigens are subjected to advanced high-throughput antibody screening technologies to discover antibodies with high specificity and affinity.

Most tumor antigens are intracellular, and our TCR-mimic platform provides a solution for developing antibodies against these valuable targets, said Dr. Yuelei Shen, Founder, Chairman and CEO of Biocytogen. TCR-mimic antibodies generated by our TCR-mimic platform have potentials to be developed into multiple drug modalities such as T cell engagers, bispecific/multispecific antibodies and CAR-T therapies. We are pleased to collaborate with FineImmune to explore the application of our antibodies in the field of cell therapies.

FineImmune is a pioneering T cell therapy company, and has solved multiple critical barriers in the microenvironment of solid tumors by using multiple proprietary technology platforms, such as GSOP for T-cell engineering, HAP for TCR identification, CMP for personalized TCR-T cell production and in vivo T-cell delivery platform (TDP). FineImmunes product pipelines include TCR-T, CAR-T, TAL, TIL, etc. The company developed the first personalized neoantigen-specific TCR-T cell therapy, which is in phase I clinical trial now. In addition, FineImmune possesses technologies for the precision prediction of the efficacy and side effects of immunotherapy, enabling healthcare professionals to provide effective and safe immunotherapy to patients with common malignant tumors.

T cells play an important role in treating cancers. Biocytogens advanced TCR-mimic platform makes it possible for us to develop T cell therapies against crucial but low-expressed intracellular tumor antigens, said Dr. Penghui Zhou, Founder and Chief Technology Officer of FineImmune. We focus on providing efficient and safe immunotherapy using advanced technologies. This collaboration will promote the development of new cell therapeutic drugs and the expansion of the potential of immunotherapy to benefit patients.

About the TCR-Mimic Platform Biocytogens T Cell Receptor (TCR)-Mimic platform utilizes HLA-expressing fully human antibody mice (HLA/RenMice) to generate antibodies to intracellular tumor-associated antigens when immunized with MHC-antigen-peptide complexes. Subsequently, Biocytogens high-throughput antibody screening platform aims to swiftly identify TCR-mimic antibodies with higher specificity and affinity than endogenous TCRs derived from patients. Currently, antibody sequences against multiple intracellular targets have been obtained, and their efficacies have been verified in vitro and in vivo. Fully human antibody sequences obtained from the TCR-mimic platform can empower the development of T cell engagers, bispecific/multispecific antibodies, and CAR-T therapies.

About BiocytogenBiocytogen Pharmaceuticals (Beijing) Co., Ltd. is a global biotechnology company that drives the research and development of novel antibody-based drugs with innovative technologies. Using its proprietary RenMabTM /RenLite mice platforms for fully human monoclonal and bispecific antibody development, Biocytogen has integrated its in vivo drug efficacy screening platforms and strong clinical development expertise to streamline the entire drug development process. Biocytogen is undertaking a large-scale project to develop antibody drugs for more than 1000 targets, known as Project Integrum, and has entered ongoing collaborations with dozens of partners worldwide to produce a variety of first-in-class and/or best-in-class antibody drugs. The company's pipeline includes 12 core products, among which two products are in phase II multi-regional clinical trials and two products are in phase I. Headquartered in Beijing, Biocytogen has branches in Haimen Jiangsu, Shanghai, Boston, USA and Heidelberg, Germany. On September 1, 2022, Biocytogen was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 02315.HK. For more information, please visit http://en.biocytogen.com.cn.

About FineImmuneGuangzhou FineImmune Biotechnology Co., Ltd. is an innovation driven company based in China. The company is mainly engaged in the development of solid tumor immunotherapy drugs and related businesses. It has solved key technical bottlenecks in solid tumor immunotherapy and possesses core technologies. A number of T-cell therapy products for solid tumors are in clinical trials, as well as diagnostic reagents for accurate identification of effective populations. It has a 2000 square meter immunotherapy R&D laboratory and a GMP production workshop for cell therapy products in Guangzhou Science City. The company's individualized TCR-T cell therapy product (new drug) has been carried out clinical research in the Affiliated Tumor Hospital of Sun Yat sen University. At present, more than 20 immune cell therapy products and technologies are under research and development. For more information, please visit http://www.fineimmu.com/.

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Biocytogen Announces Collaboration with FineImmune to Develop TCR-Mimic Antibody-Based Cell Therapy - Business Wire

DUBLIN--(BUSINESS WIRE)--The "Cell Therapy Technologies Market by Product (Media, Sera & Reagents, Cell Culture Vessels, Single Use Equipment, Systems & Software), Process (Cell Processing), Cell Type (T-cells, Stem Cells), End User (Biopharma, CMOs), Region - Global Forecast to 2027" report has been added to ResearchAndMarkets.com's offering.

The cell therapy technologies market is projected to reach USD 8.0 Billion by 2027 from USD 4.0 Billion in 2022, at a CAGR of 14.6%

The growth can be attributed to the increasing public-private partnerships. Several government and private organizations have made significant investments to strengthen R&D in cell therapy leading to a surge in cell therapy technologies demand, hence propelling market growth.

Cell therapy instruments and consumables are used in the development of novel cell therapies for the treatment of different diseases and the mass production of cells from given samples or tissues.

Cell therapy technologies find major applications in regenerative medicine, stem cell research, cancer research, and cell biology research. These technologies are also extensively used in research centers and research institutes for life science and biopharmaceutical R&D.

The rising government investments in cell-based research, increasing incidence of chronic and infectious diseases, a large number of oncology-related cell therapy clinical trials, and increasing GMP certifications for cell therapy production facilities are the key factors driving the growth of this market.

The cell preservation and distribution and handling process segment accounted for the second largest share of the market in 2021.

Cell preservation and distribution is an essential and vital step in the cell scaling-up process. In addition, with the growth in the demand for cell-based medical products and therapies, the demand for reliable storage equipment to preserve finite cell lines and cells manufactured in excess is expected to increase. This factor is expected to drive the growth of this market segment.

The CROs and CMOs accounted for the second largest share of the cell therapy technologies market in 2021.

To cater the large demand, pharmaceutical companies need to speed up clinical timelines, maintain business continuity, and free up resources for projects. This has increased outsourcing analytical tests to CROs and CMOs, thereby boosting the segment market growth.

Asia Pacific: The fastest-growing region in the cell therapy technologies market.

The Asia Pacific market is expected to register the highest CAGR during the forecast period. Some of the major factors contributing to the growth of the Asia Pacific market are low-cost manufacturing advantage, increasing per capita income, and the growing need to curb cancer. In addition, the growth of the geriatric population is also fueling the cell therapy technologies market in the region.

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Advancements in immune checkpoint inhibitors (ICIs) have revolutionized oncology therapy.1 Several ICIs targeting PD-1 or PD-L1 are available for the treatment of advanced nonsmall cell lung cancer (NSCLC).1,2 However, there remains a need for alternative treatments due to ICI resistance, failure to respond to therapy, or disease relapse.2-5 Even when ICIs are used in combination with chemotherapy, patients may experience cancer progression within 12 months.6 Oncology providers should identify opportunities for clinical trials and investigational strategies that provide options for patients with advanced NSCLC beyond ICIs and biomarker-directed therapies.

Adoptive cell therapy (ACT) is a type of immunotherapy where an individuals immune cells are harvested and expanded to help elicit a tumor-specific, cell-mediated response against cancer cells; it includes chimeric antigen receptor (CAR) T-cell therapy (CAR-T), engineered T cell receptor (TCR)-based T cell (TCR-T) immunotherapy and tumor-infiltrating lymphocytes (TILs).7 The first promising results evaluating the use of autologous (self) TILs in patients with metastatic melanoma were published in 1988, and they sparked further research.7,8

Endogenous TILs

Endogenous TILs are composed of T cells isolated from tumor tissue that can recognize tumor-specific antigens to target and attack cancer cells.9,10 In most cancers, immune infiltrate includes various macrophage subtypes and several different types of T lymphocytes.11 Helper T lymphocytes and cytotoxic T lymphocytes (CTLs) play an important role in identifying cancer cells and arresting their growth.

During tumorigenesis, genetic instability can lead to somatic mutations producing new proteins, or neoantigens, in cancer cells. Neoantigens expressed only in tumor cells are referred to as tumor-specific antigens (TSAs). All T cells, including CTLs, express a unique T-cell receptor (TCR) specific to a single TSA. Major histocompatibility complex molecules present TSAs on the tumor cell surface, which are recognized upon TCR binding. Once tumor cells are recognized as non-self, T-cell activation occurs.12,13 CTLs release cytotoxic granules, which fuse with the target cell membrane. Granulysin and perforin create pores in the cell membrane, allowing granzymes to be released into the cytoplasm. Granzymes then initiate a caspase cascade leading to apoptosis.1,14,15 However, tumor cells can initiate adaptive mechanisms to evade CTL activity, including the production of immunosuppressive cytokines that can impede the antitumor immune response.9,16 Therefore, methods to overcome immune evasion and improve upon TIL-mediated tumor cell destruction have been explored.

Development and Potential Utility of TILs for Treatment of Solid Tumors

As noted above, endogenous TILs possess TCRs with the ability to recognize and destroy tumor cells. Removing TILs from the immunosuppressive tumor environment through tumor excision allows for ex vivo assessment of antitumor activity. Once highly active TILs are identified, they are rapidly expanded to produce billions of activated, tumor-specific T cells, which are then infused back to the host to target and destroy tumor cells (Figure).13 This approach has potential utility for treating a variety of solid tumors, including NSCLC.7,17-19

Addressing Limitations of Current Treatment Strategies

TIL Therapy in Immunologically Cold Tumors

NSCLC tumors are often categorized as immunologically cold, meaning that they have features thought to impede a strong immune response, including the lack of TILs within the tumor microenvironment. This may be due to a lack of tumor antigens, defective recruitment of antigen-presenting cells, lack of T-cell costimulation and activation, and modified production of chemokines and cytokines involved in cell trafficking and activation.6,20 TIL therapy may improve immunological response within the tumor by providing more T cells to mount an attack. Moreover, TIL therapy given in combination with an ICI may help to prevent T-cell inactivation via tumor-mediated mechanisms once they have infiltrated the tumor.4,21

Limitations With Other Adoptive Cell Therapies

ACT methodologies are centered around the manipulation of an individuals own immune cells to generate a tumor-specific, cell-mediated response against cancer.7 However, CAR-T and TCR-T therapies have faced challenges in the treatment of solid tumors, including the lack of stable tumor antigen expression and the need for human leukocyte antigen restriction. Severe and unpredictable toxicities can also occur with CAR-T and TCR-T due to cross-reactivity or trace expression of tumor-associated antigens in healthy cells.22-24 Further, acquired resistance can occur following a clinical response, which may be attributed to deletion or mutation of the target antigen, antigenic heterogeneity, or impaired trafficking.6,24,25

Unlike other ACTs, TILs are composed of polyclonal cells capable of simultaneously recognizing multiple tumor antigens.19 TILs are derived from genetically unmodified host cells, which may reduce the risk for complications from immune-mediated responses. TILs are also capable of targeting truncal neoantigens clonally expressed by a cancer cell, which may reduce the risk of resistance due to deficient target antigen expression.7

Durable Remissions With TIL Therapy

TIL therapy has the potential for durable, complete remissions.26 This partially is due to the transdifferentiation potential and lifespan of memory T cells.6 Such responses have been observed in heavily pretreated patients with metastatic melanoma after disease progression following treatment with chemotherapy, IL-2, antiCTLA-4 monoclonal antibodies, or a combination of these.26 Additionally, durable remissions following TIL therapy have been reported in a variety of other solid tumor types, including cholangiocarcinoma and cervical, colorectal, and breast cancers.27-30

Future Directions

Clinical trials in metastatic melanoma have demonstrated complete and durable responses from TIL therapy, even in patients who progressed on multiple prior therapies, including antiPD-1 agents.31,32 These findings suggest that TIL therapy may be a viable option for patients with PD-1 resistance or in cancers with lower immunogenicity. Observed similarities between NSCLC and melanoma suggest a role for TIL therapy in the treatment of NSCLC and warrant further investigation.

For information regarding advancements in TIL therapy, resources and further information are available from TILs Working Group at https://www.tilsinbreastcancer.org/.

References

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2. Horvath L, Thienpont B, Zhao L, Wolf D, Pircher A. Overcoming immunotherapy resistance in non-small cell lung cancer (NSCLC) - novel approaches and future outlook.Mol Cancer. 2020;19(1):141. doi:10.1186/s12943-020-01260-z

3. Nowicki TS, Hu-Lieskovan S, Ribas A. Mechanisms of resistance to PD-1 and PD-L1 blockade.Cancer J. 2018;24(1):47-53. doi:10.1097/PPO.0000000000000303

4. Adoptive cell therapy plus checkpoint inhibitors show promise in non-small cell lung cancer. New release. Moffitt Cancer Center. August 12, 2021. Accessed July 29, 2022. https://moffitt.org/newsroom/press-release-archive/adoptive-cell-therapy-plus-checkpoint-inhibitors-show-promise-in-non-small-cell-lung-cancer/

5. Pathak R, Pharaon RR, Mohanty A, Villaflor VM, Salgia R, Massarelli E. Acquired resistance to PD-1/PD-L1 blockade in lung cancer: mechanisms and patterns of failure.Cancers (Basel). 2020;12(12):3851. doi:10.3390/cancers12123851

6. Creelan BC, Wang C, Teer JK, et al. Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial.Nat Med. 2021;27(8):1410-1418. doi:10.1038/s41591-021-01462-y

7. Hulen TM, Chamberlain CA, Svane IM, Met O. ACT up TIL now: the evolution of tumor-infiltrating lymphocytes in adoptive cell therapy for the treatment of solid tumors. Immuno. 2022;1(3):194-211. doi:10.3390/immuno1030012

8. Rosenberg SA, Packard BS, Aebersold PM, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report.N Engl J Med. 1988;319(25):1676-1680. doi:10.1056/NEJM198812223192527

9. Zur RT, Adler G, Shamalov K, et al. Adoptive T-cell immunotherapy: perfecting self-defenses. In: Klink M, Szulc-Kielbik I, eds. Interaction of Immune and Cancer Cells. Springer International Publishing AG; 2022:253-294.

10. Investigational TIL Therapy. Iovance Biotherapeutics. 2022. Accessed September 8, 2022. https://www.iovance.com/about-til/

11. Linette GP, Carreno BM. Tumor-infiltrating lymphocytes in the checkpoint inhibitor era.Curr Hematol Malig Rep. 2019;14(4):286-291. doi:10.1007/s11899-019-00523-x

12. Zhang Z, Lu M, Qin Y, et al. Neoantigen: a new breakthrough in tumor immunotherapy.Front Immunol. 2021;12:672356. doi:10.3389/fimmu.2021.672356

13. Qin SS, Melucci AD, Chacon AC, Prieto PA. Adoptive T cell therapy for solid tumors: pathway to personalized standard of care.Cells. 2021;10(4):808. doi:10.3390/cells10040808

14. Cullen SP, Brunet M, Martin SJ. Granzymes in cancer and immunity.Cell Death Differ. 2010;17(4):616-623. doi:10.1038/cdd.2009.206

15. Nirmala JG, Lopus M. Cell death mechanisms in eukaryotes.Cell Biol Toxicol. 2020;36(2):145-164. doi:10.1007/s10565-019-09496-2

16. Vinay DS, Ryan EP, Pawelec G, et al. Immune evasion in cancer: mechanistic basis and therapeutic strategies.Semin Cancer Biol. 2015;35(suppl):S185-S198. doi:10.1016/j.semcancer.2015.03.004

17. Sarnaik AA, Hamid O, Khushalani NI, et al. Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. J Clin Oncol. 2021;39(24):2656-2666. doi:10.1200/JCO.21.00612

18. Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response.Nat Rev Immunol. 2012;12(4):269-281. doi:10.1038/nri3191

19. Wang S, Sun J, Chen K, Ma P, et al. Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors.BMC Med. 2021;19(1):140. doi:10.1186/s12916-021-02006-4

20. Bonaventura P, Shekarian T, Alcazer V, et al. Cold tumors: a therapeutic challenge for immunotherapy.Front Immunol. 2019;10:168. doi:10.3389/fimmu.2019.00168

21. Lanitis E, Dangaj D, Irving M, Coukos G. Mechanisms regulating T-cell infiltration and activity in solid tumors.Ann Oncol. 2017;28(suppl 12):xii18-xii32. doi:10.1093/annonc/mdx238

22. Blumenschein GR, Devarakonda S, Johnson M, et al. Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10+advanced non-small cell lung cancer.J Immunother Cancer. 2022;10(1):e003581. doi:10.1136/jitc-2021-003581

23. Duinkerken CW, Rohaan MW, de Weger VA, et al. Sensorineural hearing loss after adoptive cell immunotherapy for melanoma using MART-1 specific T cells: a case report and its pathophysiology.Otol Neurotol. 2019;40(7):e674-e678. doi:10.1097/MAO.0000000000002332

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25. Haas AR, Tanyi JL, O'Hara MH, et al. Phase I study of lentiviral-transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers.Mol Ther. 2019;27(11):1919-1929. doi:10.1016/j.ymthe.2019.07.015

26. Rosenberg SA, Yang JC, Sherry RM, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy.Clin Cancer Res. 2011;17(13):4550-4557. doi:10.1158/1078-0432.CCR-11-0116

27. Zacharakis N, Chinnasamy H, Black M, et al. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer.Nat Med. 2018;24(6):724-730. doi:10.1038/s41591-018-0040-8

28. Stevanovi S, Draper LM, Langhan MM, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells.J Clin Oncol. 2015;33(14):1543-1550. doi:10.1200/JCO.2014.58.9093

29. Tran E, Robbins PF, Lu YC, et al. T-cell transfer therapy targeting mutant KRAS in cancer.N Engl J Med. 2016;375(23):2255-2262. doi:10.1056/NEJMoa1609279

30. Tran E, Turcotte S, Gros A, et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer.Science. 2014;344(6184):641-645. doi:10.1126/science.1251102

31. Robertson J, Salm M, Dangl M. Adoptive cell therapy with tumour-infiltrating lymphocytes: the emerging importance of clonal neoantigen targets for next-generation products in non-small cell lung cancer.Immunooncol Technol. 2019;3:1-7. doi:10.1016/j.iotech.2019.09.003

32. Dafni U, Michielin O, Lluesma SM, et al. Efficacy of adoptive therapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 in advanced cutaneous melanoma: a systematic review and meta-analysis.Ann Oncol. 2019;30(12):1902-1913. doi:10.1093/annonc/mdz398

Figure. Development Process of TIL Therapy for Solid Tumors13

TIL, tumor-infiltrating lymphocyte.

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TIL Therapy as a Personalized Treatment Strategy for NSCLC - Targeted Oncology