Category Archives: Cell Therapy

Meet the new medicines, page 5

In CAR-T cell therapy, immune cells are removed from a patient, genetically modified, then put back into the patient to fight against cancer. This approach has met with substantial success against blood cancers. For example, one CAR-T cell therapy, approved in August 2017, is now being used to treat children with acute lymphoblastic leukemia.

In cell transplants, patients are given functional cells as a replacement. When patients with blood cancers undergo chemotherapy, their blood stem cells get destroyed. Afterward, they receive a transplant of blood stem cells collected either from themselves before chemotherapy or from a separate donor so that they can continue to make blood.

Examples of cell replacement therapies that are in the early stages of clinical study include:

A different type of cell therapy takes advantage of certain cell properties to deliver drugs. For example, cancer cells have a self-homing ability, moving around the body to find tumors and spread. An HSCI scientist has co-opted this ability, using cancer cells to deliver tumor-killing proteins.

Another example is mesenchymal stem cells, which are attracted by inflammation and can home to a site of injury. They can be used to deliver small-molecule or biologic drugs.

Many cell therapies that have reached the stage of clinical trials are bespoke to each patient. Because the cells come from patients themselves, this is referred to as autologous.

Because of this, manufacturing is never done in bulk quantities just one batch per patient. This process needs to be highly controlled and accurate, and the success rate extraordinarily high for a very small number of patients. However, it is currently a very expensive process, in part because each product made is the full run.

Other types of cell therapies make use of cells from another person, and are called allogeneic. The manufacturing and regulatory advantage is having a product that can cover many people. But the medical risk is that the cells will be identified as foreign and rejected by the immune system in the absence of a way to protect the them from the immune attack.

HSCI scientists are working on a couple of ways to create cell therapies that would not be rejected by the immune system:

If cell therapy is ever going to be available to large numbers of people, we will need disruptive breakthroughs in academic, commercial, and industrial research and development.

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Cell therapies | Harvard Stem Cell Institute (HSCI)

SAN DIEGO, April 13, 2023 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today announced that two key industry opinion leaders and management will participate in Oppenheimer & Co.’s Virtual Fireside Chat: Discussion of ROR1 CAR-T Cell Therapy in Hematological Malignancies and Solid Tumors on Tuesday, April 18, 2023 at 1:30 p.m. EDT.

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Oncternal Therapeutics Participating in Oppenheimer & Co.’s Virtual Fireside Chat: Discussion of ROR1 CAR T Cell Therapy in Hematological...

Approved oral medications

Two oral medications are FDA-approved for treating adults with very rare cases of advanced BCC that are large or have penetrated the skin deeply, spread to other parts of the body or resisted multiple treatments and recurred.

Vismodegib (Erivedge)Sonidegib (Odomzo)

Both medications are targeted drugs taken by mouth. They work by blocking the hedgehog signaling pathway, a key factor in the development of BCC. In 2012, vismodegib became the first medicine ever approved by the FDA for treating advanced BCC. A second hedgehog pathway inhibitor (HHI) drug, sonidegib, was approved for advanced BCC in 2015.

Vismodegib is used for the extraordinarily rare cases of metastatic BCC or locally advanced BCC (tumors that have penetrated the skin deeply or frequently recurred) that either recur after surgery or radiation, or cannot be treated with surgery or radiation and have become dangerous or life-threatening.

Sonidegib is used in adults with BCC that is locally advanced, penetrating the skin deeply or repeatedly recurring, as well as in cases when other treatments such as surgery or radiation cannot be used.

Due to a risk of birth defects, women who are pregnant or may become pregnant should not use either drug. Couples must use birth control if the woman is capable of becoming pregnant while her partner is taking the medication.

Scientists are also investigating several other targeted hedgehog inhibitors as potential treatments for locally advanced and metastatic BCC.

In February 2021, the U.S. Food and Drug Administration (FDA) approved the intravenous immunotherapy medication,cemiplimab-rwlc(Libtayo) for treating patients with certain forms of advanced basal cell carcinoma.

Cemiplimab-rwlc(Libtayo)

Cemiplimabis a type of immunotherapy known as a checkpoint blockade therapy, which works by harnessing the power of the immune system to battle cancer. Under normal conditions, the immune system uses checkpoints, which are molecules that suppress production of T cells, the white blood cells that help protect the body from infection. These checkpoints keep T cells from overproducing and attacking normal cells in the body. However, cancer cells have the ability to keep those checkpoints active, suppressing the immune system so the cancer can grow and thrive. Cemiplimabblocks a particular checkpoint called PD-1 from working, so the immune system can releasemassive amounts of T cells to attack and kill cancer cells.

Find out more aboutcemiplimab.

Cemiplimabis used to treat patients with advanced basal cell carcinoma (BCC) previously treated with a hedgehog pathway inhibitor (HHI) or for whom an HHI is not appropriate. Full approval was granted for patients with locally advanced BCC and accelerated approval was granted for patients with metastatic BCC.

Link:
Basal Cell Carcinoma Treatment - The Skin Cancer Foundation

How Cellular Immunotherapies Are Changing the Outlook for Cancer Patients

Reviewed By:

Philip D. Greenberg, MD.Fred Hutchinson Cancer Research Center

Some of these approaches involve directly isolating our own immune cells and simply expanding their numbers, whereas others involve genetically engineering our immune cells (via gene therapy) to enhance their cancer-fighting capabilities.

Our immune system is capable of recognizing and eliminating cells that have become infected or damaged as well as those that have become cancerous. In the case of cancer, immune cells known as killer T cells are particularly powerful against cancer, due to their ability to bind to markers known as antigens on the surface of cancer cells. Cellular immunotherapies take advantage of this natural ability and can be deployed in different ways:

Today, cell therapies are constantly evolving and improving and providing new options to cancer patients. Cell therapies are currently being evaluated, both alone and in combination with other treatments, in a variety of cancer types in clinical trials.

Cancer patients have naturally occurring T cells that are often capable of targeting their cancer cells. These T cells are some of the most powerful immune cells in our body, and come in several types. The killer T cells, especially, are capable of recognizing and eliminating cancer cells in a very precise way.

The existence of these T cells alone, however, isnt always enough to guarantee that they will be able to carry out their mission to eliminate tumors. One potential roadblock is that these T cells must first become activated before they can effectively kill cancer cells, and then they must be able to maintain that activity for a sufficiently long time to sustain an effective anti-tumor response. Another is that these T cells might not exist in sufficient numbers.

One form of adoptive cell therapy that attempts to address these issues is called tumor-infiltrating lymphocyte (TIL) therapy. This approach harvests naturally occurring T cells that have already infiltrated patients tumors, and then activates and expands them. Then, large numbers of these activated T cells are re-infused into patients, where they can then seek out and destroy tumors.

Unfortunately, not all patients have T cells that have already recognized their tumors. Others patients might, but for a number of reasons, these T cells may not be capable of being activated and expanded to sufficient numbers to enable rejection of their tumors. For these patients, doctors may employ an approach known as engineered T cell receptor (TCR) therapy.

This approach also involves taking T cells from patients, but instead of just activating and expanding the available anti-tumor T cells, the T cells can also be equipped with a new T cell receptor that enables them to target specific cancer antigens. By allowing doctors to choose an optimal target for each patients tumor and distinct types of T cell to engineer, the treatment can be further personalized to individuals and, ideally, provide patients with greater hope for relief.

The previously mentioned TIL and TCR therapies can only target and eliminate cancer cells that present their antigens in a certain context (when the antigens are bound by the major histocompatibility complex, or MHC).

Recent advances in cell-based immunotherapy have enabled doctors to overcome this limitation. Scientists equip a patients T cells with a synthetic receptor known as a CAR, which stands for chimeric antigen receptor.

A key advantage of CARs is their ability to bind to cancer cells even if their antigens arent presented on the surface via MHC, which can render more cancer cells vulnerable to their attacks. However, CAR T cells can only recognize antigens that themselves are naturally expressed on the cell surface, so the range of potential antigen targets is smaller than with TCRs. In October 2017, the U.S. Food and Drug Administration (FDA) approved the first CAR T cell therapy to treat adults with certain types of large B-cell lymphoma.

Given their power, CARs are being explored in a variety of strategies for many cancer types. One approach currently in clinical trials is using stem cells to create a limitless source of off-the-shelf CAR T cells. This may have application to only selected settings, but could allow doctors to treat patients in a timelier fashion.

More recently, adoptive cell therapy strategies have begun to incorporate other immune cells, such as Natural Killer (NK) cells. One application being explored in the clinic involves equipping these NK cells with cancer-targeting CARs.

There are currently two adoptive cell therapies that are approved by the FDA for the treatment of cancer.

Side effects may vary according to the type of adoptive cell immunotherapyand what exactly it targetsand may also be influenced by the location and type of cancer as well as a patients overall health. Potential cell therapy-related side effects often take the form of an overactive immune response and may lead to excessive inflammation via cytokine release syndrome (also known as cytokine storm), and also to neurotoxicity from inflammation in the brain. Side effects can range from mild to moderate and may become potentially life-threatening under certain circumstances.

Fortunately, in most cases, potential immunotherapy-related side effects can be managed safely as long as the potential side effects are recognized and addressed early. Therefore, its extremely important that patients inform their medical care team as soon as possible if they experience any unusual symptoms during or after treatment with cancer immunotherapy. In addition, patients should always consult their doctors and the rest of their care team to gain a better and fuller understanding of the potential risks and side effects associated with specific adoptive cell immunotherapies.

Common side effects associated with currently approved adoptive cell therapies may include but are not limited to: acute kidney injury, bleeding episodes, heart arrhythmias, chills, constipation, cough, cytokine release syndrome (cytokine storm), decreased appetite, delirium, diarrhea, dizziness, edema, encephalopathy, fatigue, febrile neutropenia, fever, headache, hypogammaglobulinemia, hypotension, hypoxia, infections, nausea, neurotoxicity, pyrexia, tachycardia, tremors, and vomiting.

Throughout its history, CRI has supported a variety of basic research projects aimed at improving our understanding of the identity and functions of our many immune cells as well as translational and clinical efforts that seek to use these insights in the development of cellular immunotherapies for cancer patients in the clinic.

Some of the most important contributions made by CRI scientists in the area of adoptive cell therapy include:

Go here to see the original:
Adoptive Cell Therapy - Cancer Research Institute (CRI)

National Medical Commission prohibits use of stem cell therapy to treat patients with autism  Hindustan Times

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National Medical Commission prohibits use of stem cell therapy to treat patients with autism - Hindustan Times

Wang S, Sun J, Chen K, et al. Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors. BMC Med. 2021;19(1):140.

Article Google Scholar

Singh AK, McGuirk JP. CAR T cells: continuation in a revolution of immunotherapy. Lancet Oncol. 2020;21(3):e16878. https://doi.org/10.1016/S1470-2045(19)30823-X.

Article CAS PubMed Google Scholar

Newick K, O'Brien S, Moon E, et al. CAR T cell therapy for solid tumors. Annu Rev Med. 2017;68:13952. https://doi.org/10.1146/annurev-med-062315-120245.

Article CAS PubMed Google Scholar

Zhang C, Liu J, Zhong JF, et al. Engineering CAR-T cells. Biomark Res. 2017;5:22. https://doi.org/10.1186/s40364-017-0102-y.

Article PubMed PubMed Central Google Scholar

Sadelain M, Brentjens R, Rivire I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3(4):38898. https://doi.org/10.1158/2159-8290.CD-12-0548.

Article CAS PubMed PubMed Central Google Scholar

van der Stegen SJ, Hamieh M, Sadelain M. The pharmacology of second-generation chimeric antigen receptors. Nat Rev Drug Discov. 2015;14(7):499509. https://doi.org/10.1038/nrd4597.

Article CAS PubMed PubMed Central Google Scholar

Marin V, Pizzitola I, Agostoni V, et al. Cytokine-induced killer cells for cell therapy of acute myeloid leukemia: improvement of their immune activity by expression of CD33-specific chimeric receptors. Haematologica. 2010;95(12):214452. https://doi.org/10.3324/haematol.2010.026310.

Article CAS PubMed PubMed Central Google Scholar

Roselli E, Boucher JC, Li G, et al. 4-1BB and optimized CD28 co-stimulation enhances function of human mono-specific and bi-specific third-generation CAR T cells. J Immunother Cancer. 2021;9(10). https://doi.org/10.1136/jitc-2021-003354.

Huang R, Li X, He Y, et al. Recent advances in CAR-T cell engineering. J Hematol Oncol. 2020;13(1):86. https://doi.org/10.1186/s13045-020-00910-5.

Article CAS PubMed PubMed Central Google Scholar

Chmielewski M, Abken H. TRUCKs: the fourth generation of CARs. Expert Opin Biol Ther. 2015;15(8):114554. https://doi.org/10.1517/14712598.2015.1046430.

Article CAS PubMed Google Scholar

Cho JH, Collins JJ, Wong WW. Universal chimeric antigen receptors for multiplexed and logical control of T cell responses. Cell. 2018;173(6):14261438.e11. https://doi.org/10.1016/j.cell.2018.03.038.

Article CAS PubMed PubMed Central Google Scholar

Urbanska K, Lanitis E, Poussin M, et al. A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. Cancer Res. 2012;72(7):184452. https://doi.org/10.1158/0008-5472.CAN-11-3890.

Article CAS PubMed PubMed Central Google Scholar

Ma JS, Kim JY, Kazane SA, et al. Versatile strategy for controlling the specificity and activity of engineered T cells. Proc Natl Acad Sci U S A. 2016;113(4):E4508. https://doi.org/10.1073/pnas.1524193113.

Article CAS PubMed PubMed Central Google Scholar

Xie YJ, Dougan M, Jailkhani N, et al. Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice. Proc Natl Acad Sci U S A. 2019;116(16):762431. https://doi.org/10.1073/pnas.1817147116.

Article CAS PubMed PubMed Central Google Scholar

Long AH, Haso WM, Shern JF, et al. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med. 2015;21(6):58190. https://doi.org/10.1038/nm.3838.

Article CAS PubMed PubMed Central Google Scholar

Weatherill EE, Cain KL, Heywood SP, et al. Towards a universal disulphide stabilised single chain Fv format: importance of interchain disulphide bond location and vL-vH orientation. Protein Eng Des Sel. 2012;25(7):3219. https://doi.org/10.1093/protein/gzs021.

Article CAS PubMed Google Scholar

Zhylko A, Winiarska M, Graczyk-Jarzynka A. The great war of today: modifications of CAR-T cells to effectively combat malignancies. Cancers (Basel). 2020;12(8). https://doi.org/10.3390/cancers12082030.

Wei J, Han X, Bo J, et al. Target selection for CAR-T therapy. J Hematol Oncol. 2019;12(1):62. https://doi.org/10.1186/s13045-019-0758-x.

Article PubMed PubMed Central Google Scholar

Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):18008. https://doi.org/10.1182/blood-2017-03-769620.

Article CAS PubMed PubMed Central Google Scholar

Mounier N, Canals C, Gisselbrecht C, et al. High-dose therapy and autologous stem cell transplantation in first relapse for diffuse large B cell lymphoma in the rituximab era: an analysis based on data from the European blood and marrow transplantation registry. Biol Blood Marrow Transplant. 2012;18(5):78893. https://doi.org/10.1016/j.bbmt.2011.10.010.

Article PubMed Google Scholar

Scheuermann RH, Racila E. CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk Lymphoma. 1995;18(5-6):38597. https://doi.org/10.3109/10428199509059636.

Article CAS PubMed Google Scholar

Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):4556.

Article CAS Google Scholar

Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet (London, England). 2020;396(10254):83952.

Article Google Scholar

Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene Ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):253144.

Article CAS Google Scholar

Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):64054. https://doi.org/10.1056/NEJMoa2116133.

Article CAS PubMed Google Scholar

Neelapu SS, Dickinson M, Munoz J, et al. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nat Med. 2022;28(4):73542. https://doi.org/10.1038/s41591-022-01731-4.

Article CAS PubMed PubMed Central Google Scholar

Ghione P, Palomba ML, Patel A, et al. Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Blood. 2022. https://doi.org/10.1182/blood.2021014375.

Jacobson CA, Chavez JC, Sehgal AR, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(1):91103. https://doi.org/10.1016/S1470-2045(21)00591-X.

Article CAS PubMed Google Scholar

Grommes C, DeAngelis LM. Primary CNS lymphoma. J Clin Oncol. 2017;35(21):24108. https://doi.org/10.1200/JCO.2017.72.7602.

Article CAS PubMed PubMed Central Google Scholar

Frigault MJ, Dietrich J, Gallagher K, et al. Safety and efficacy of tisagenlecleucel in primary CNS lymphoma: a phase 1/2 clinical trial. Blood. 2022;139(15):230615. https://doi.org/10.1182/blood.2021014738.

Article CAS PubMed Google Scholar

Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382(14):133142. https://doi.org/10.1056/NEJMoa1914347.

Article CAS PubMed PubMed Central Google Scholar

Miles RR, Arnold S, Cairo MS. Risk factors and treatment of childhood and adolescent Burkitt lymphoma/leukaemia. Br J Haematol. 2012;156(6):73043. https://doi.org/10.1111/j.1365-2141.2011.09024.x.

Article CAS PubMed Google Scholar

Russo-Carbolante EM, Picano-Castro V, Alves DC, et al. Integration pattern of HIV-1 based lentiviral vector carrying recombinant coagulation factor VIII in Sk-Hep and 293T cells. Biotechnol Lett. 2011;33(1):2331. https://doi.org/10.1007/s10529-010-0387-5.

Article CAS PubMed Google Scholar

Tao J, Zhou X, Jiang Z. cGAS-cGAMP-STING: the three musketeers of cytosolic DNA sensing and signaling. IUBMB Life. 2016;68(11):85870. https://doi.org/10.1002/iub.1566.

Article CAS PubMed Google Scholar

Gndara C, Affleck V, Stoll EA. Manufacture of third-generation lentivirus for preclinical use, with process development considerations for translation to good manufacturing practice. Hum Gene Ther Methods. 2018;29(1):115. https://doi.org/10.1089/hgtb.2017.098.

Article CAS PubMed PubMed Central Google Scholar

Atianand MK, Fitzgerald KA. Molecular basis of DNA recognition in the immune system. J Immunol. 2013;190(5):19118. https://doi.org/10.4049/jimmunol.1203162.

Article CAS PubMed Google Scholar

Michieletto D, Lusic M, Marenduzzo D, et al. Physical principles of retroviral integration in the human genome. Nat Commun. 2019;10(1):575. https://doi.org/10.1038/s41467-019-08333-8.

Article CAS PubMed PubMed Central Google Scholar

Zhang J, Hu Y, Yang J, et al. Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL. Nature. 2022. https://doi.org/10.1038/s41586-022-05140-y.

Doody GM, Justement LB, Delibrias CC, et al. A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP. Science. 1995;269(5221):2424. https://doi.org/10.1126/science.7618087.

Article CAS PubMed Google Scholar

Baird JH, Frank MJ, Craig J, et al. CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma. Blood. 2021;137(17):23215. https://doi.org/10.1182/blood.2020009432.

Article CAS PubMed PubMed Central Google Scholar

Zhang WY, Wang Y, Guo YL, et al. Treatment of CD20-directed chimeric antigen receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. Signal transduction and targeted. Therapy. 2016;1:16002.

Google Scholar

Till BG, Jensen MC, Wang J, et al. CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. BLOOD. 2012;119(17):394050.

Article CAS Google Scholar

Du J, Zhang Y. Sequential anti-CD19, 22, and 20 autologous chimeric antigen receptor T-cell (CAR-T) treatments of a child with relapsed refractory Burkitt lymphoma: a case report and literature review. J Cancer Res Clin Oncol. 2020;146(6):157582. https://doi.org/10.1007/s00432-020-03198-7.

Article CAS PubMed Google Scholar

Ramos CA, Savoldo B, Torrano V, et al. Clinical responses with T lymphocytes targeting malignancy-associated light chains. J Clin Invest. 2016;126(7):258896. https://doi.org/10.1172/JCI86000.

Article PubMed PubMed Central Google Scholar

Ranganathan R, Shou P, Ahn S, et al. CAR T cells targeting human immunoglobulin light chains eradicate mature B-cell malignancies while sparing a subset of Normal B cells. Clin Cancer Res. 2021;27(21):595160. https://doi.org/10.1158/1078-0432.CCR-20-2754.

Article CAS PubMed PubMed Central Google Scholar

Bunse M, Pfeilschifter J, Bluhm J, et al. CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin's lymphoma and tumor-supportive follicular T helper cells. Nat Commun. 2021;12(1):240. https://doi.org/10.1038/s41467-020-20488-3.

Article CAS PubMed PubMed Central Google Scholar

Spiegel JY, Patel S, Muffly L, et al. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med. 2021;27(8):141931. https://doi.org/10.1038/s41591-021-01436-0.

Article CAS PubMed PubMed Central Google Scholar

Zhang Y, Li J, Lou X, et al. A prospective investigation of bispecific CD19/22 CAR T cell therapy in patients with relapsed or refractory B cell non-Hodgkin lymphoma. Front Oncol. 2021;11:664421. https://doi.org/10.3389/fonc.2021.664421.

Article PubMed PubMed Central Google Scholar

Wei G, Zhang Y, Zhao H, et al. CD19/CD22 dual-targeted CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphoma: a safety and efficacy study. Cancer Immunol Res. 2021;9(9):106170. https://doi.org/10.1158/2326-6066.CIR-20-0675.

Article CAS PubMed Google Scholar

Tong C, Zhang Y, Liu Y, et al. Optimized tandem CD19/CD20 CAR-engineered T cells in refractory/relapsed B-cell lymphoma. Blood. 2020;136(14):163244. https://doi.org/10.1182/blood.2020005278.

Article PubMed PubMed Central Google Scholar

Shah NN, Johnson BD, Schneider D, et al. Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial. Nat Med. 2020;26(10):156975. https://doi.org/10.1038/s41591-020-1081-3.

Article CAS PubMed Google Scholar

Safarzadeh Kozani P, Safarzadeh Kozani P, Rahbarizadeh F. CAR-T cell therapy in T-cell malignancies: is success a low-hanging fruit? Stem Cell Res Ther. 2021;12(1):527. https://doi.org/10.1186/s13287-021-02595-0.

Article CAS PubMed PubMed Central Google Scholar

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Tumor buster - where will the CAR-T cell therapy missile go?

1. Gilead lands new cell therapy for Kite in $225M Arcellx deal, providing global scale for future J&J-Legend showdown  FierceBiotech
2. Gilead buys into multiple myeloma cell therapy with Arcellx deal  BioPharma Dive
3. Gilead Sciences Gets a Shot at Next-Gen Cell Therapy With $325M Arcellx Alliance  MedCity News
4. Kite and Arcellx Announce Strategic Collaboration to Co-develop and Co-commercialize Late-stage Clinical CART-ddBCMA in Multiple Myeloma  Gilead Sciences
5. Gilead Sciences' Kite, Arcellx to Develop, Commercialize Cell Therapy Treatment for Multiple Myeloma  Marketscreener.com
6. View Full Coverage on Google News

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Gilead lands new cell therapy for Kite in $225M Arcellx deal, providing global scale for future J&J-Legend showdown - FierceBiotech

What is chimeric antigen receptor (CAR)-T cell therapy?

CAR-T cell therapy is a kind of immunotherapy. It involves harnessing the power of a person's own immune system by engineering T cells to recognize and destroy cancer cells.

The FDA-approved conditions for CAR-T cell therapy include:

In order to be eligible for CAR-T cell therapy, typically you must have already received standard of care chemotherapies. Mayo Clinic doctors will evaluate you to understand how to best treat your disease and to understand if CAR-T cell therapy may be an option.

If you think you or a loved one is eligible for CAR-T cell therapy at one of Mayo Clinic's three locations, please call the phone number below to request an appointment at the location you are interested in seeking care at. Our appointment staff will work to find the specialist who can best address your questions and needs. Be sure to mention that you are interested in CAR-T cell therapy to ensure your request is routed correctly.

Mayo Clinic hematologists are happy to discuss possible referrals with doctors and allied health staff outside of Mayo Clinic. Your doctor needs to mention that you are interested in understanding whether CAR-T cell therapy may be appropriate for you. Patient appointments are scheduled Monday through Friday from 8 a.m. to 5 p.m. local time at each campus. Consultations with Mayo doctors are also available during these hours.

Minnesota: Have your doctor call the Hematology Department directly at 507-284-8707 to request an appointment for a consultation. Your doctor can also contact the Referring Provider Service (toll-free) at 800-533-1564.

Arizona: Have your doctor call the Hematology Department directly at 480-342-4800 to request an appointment for a consultation. Your doctor can also contact the Referring Provider Service (toll-free) at 866-629-6362.

Florida: Have your doctor call the Hematology Department directly at 904-956-3309 to request an appointment for a consultation. Your doctor can also contact the Referring Provider Service (toll-free) at 800-634-1417.

Mayo Clinic is typically able to offer you an appointment within one to two weeks with a provider who specializes in the type of cancer or medical condition you have. Once you have been evaluated by the necessary specialists and determined to be eligible for CAR-T cell therapy, Mayo Clinic will work with you to schedule treatment. The appointment time depends on several factors, including your condition, laboratory capacity and the number of people seeking this treatment.

CAR-T cell therapy is a newer type of cancer treatment that may be more expensive than other therapies. Not all insurance policies cover CAR-T cell therapy. The out-of-pocket cost for CAR-T cell therapy varies, depending on your insurance coverage for services at Mayo Clinic as well as for CAR-T cell therapy itself.

In order to determine if your insurance company will cover CAR-T cell therapy, please call your insurance company and ask the following two questions:

We will work with you and your health insurance company to determine if CAR-T cell therapy will be covered, if that is the recommended treatment. This includes any appeals process with the insurance company.

During your CAR-T cell therapy, you may not be able to do things you can normally do for yourself well or safely. A caregiver helps you get through this process. The caregiver provides physical and emotional support and, sometimes, acts as an advocate for you.

Some tasks a caregiver might do for you:

The caregiver also needs to be your cheerleader, someone to give you words of encouragement, keep you going, cheer you up, make you laugh and help you get through it all.

Once you have been identified as a candidate for CAR-T cell therapy, you may need to make several trips to Mayo Clinic to determine your eligibility for the therapy as well as to meet with a doctor to make a plan for your care.

Evaluation: For this initial evaluation, plan on staying near Mayo Clinic for up to five business days in order to complete needed tests.

Collection: Depending on the timing of insurance approval, the collection may occur as soon as the week following the completion of evaluation. The collection process will take a minimum of two days.

Processing: Most people return home during this phase.

Chemotherapy before infusion: From this point on, plan on being at Mayo Clinic for many weeks depending on your medical needs. During this time, you'll need to stay within 30 minutes of Mayo Clinic.

Infusion: The infusion of CAR-T cells typically takes 30 to 90 minutes. However, plan for the infusion visit to take up to six hours to allow for care before and after the infusion.

Care after infusion: You will be monitored closely for many weeks after the CAR-T cell infusion.

Initially, after your CAR-T cell therapy, you will have appointments with the Mayo Clinic team as frequently as every month. As your health improves and there are fewer signs of disease, the appointments will become less frequent. Anticipate at least annual visits to Mayo Clinic.

Because CAR-T cell therapy is a form of gene therapy, the FDA requires a 15-year monitoring.

We want to help make your travel to Mayo Clinic as easy as possible. We provide information and a variety of services to help.

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At Mayo Clinic, the needs of the patient come first. The CAR-T Cell Therapy Program doctors and other specialists consult with their colleagues about your condition and recommend treatment options based on their experience and evidence-based medicine. Mayo Clinic's experts have treated people in the landmark clinical trial that led to FDA approval of this innovative therapy. This program is one of a very few such programs at select medical centers with experts trained and certified to manage CAR-T cell therapy as clinical practice.

Feb. 19, 2022

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CAR-T Cell Therapy Program - Frequently asked questions

Nine types of standard treatment are used:Surgery

Four types of surgery are used to treat lung cancer:

After the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

Stereotactic body radiation therapy is a type of external radiation therapy. Special equipment is used to place the patient in the same position for each radiation treatment. Once a day for several days, a radiation machine aims a larger than usual dose of radiation directly at the tumor. By having the patient in the same position for each treatment, there is less damage to nearby healthy tissue. This procedure is also called stereotactic external-beam radiation therapy and stereotaxic radiation therapy.

Stereotactic radiosurgery is a type of external radiation therapy used to treat lung cancer that has spread to the brain. A rigid head frame is attached to the skull to keep the head still during the radiation treatment. A machine aims a single large dose of radiation directly at the tumor in the brain. This procedure does not involve surgery. It is also called stereotaxic radiosurgery, radiosurgery, and radiation surgery.

For tumors in the airways, radiation is given directly to the tumor through an endoscope.

The way the radiation therapy is given depends on the type and stage of the cancer being treated.It also depends on where the cancer is found. External and internal radiation therapy are used to treat non-small cell lung cancer.

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy).

The way the chemotherapy is given depends on the type and stage of the cancer being treated.

See Drugs Approved for Non-Small Cell Lung Cancer for more information.

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. Targeted therapies usually cause less harm to normal cells than chemotherapy or radiation therapy do. Monoclonal antibodies, tyrosine kinase inhibitors, and mammalian target of rapamycin (mTOR) inhibitors are three types of targeted therapy being used to treat advanced, metastatic, or recurrent non-small cell lung cancer.

Monoclonal antibodies

Monoclonal antibodies are immune system proteins made in the laboratory to treat many diseases, including cancer. As a cancer treatment, these antibodies can attach to a specific target on cancer cells or other cells that may help cancer cells grow. The antibodies are able to then kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.

There are different types of monoclonal antibody therapy:

Tyrosine kinase inhibitors

Tyrosine kinase inhibitors are small-molecule drugs that go through the cell membrane and work inside cancer cells to block signals that cancer cells need to grow and divide. Some tyrosine kinase inhibitors also have angiogenesis inhibitor effects.

There are different types of tyrosine kinase inhibitors:

Mammalian target of rapamycin (mTOR) inhibitors

mTOR inhibitors block a protein called mTOR, which may keep cancer cells from growing and prevent the growth of new blood vessels that tumors need to grow. Everolimus is a type of mTOR inhibitor.

See Drugs Approved for Non-Small Cell Lung Cancer for more information.

Immunotherapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This cancer treatment is a type of biologic therapy.

Immune checkpoint inhibitor therapy is a type of immunotherapy used to treat some patients with advanced non-small-cell lung cancer.

Types of immune checkpoint inhibitor therapy include:

See Drugs Approved for Non-Small Cell Lung Cancer for more information.

Laser therapy is a cancer treatment that uses a laser beam (a narrow beam of intense light) to kill cancer cells.

Photodynamic therapy (PDT) is a cancer treatment that uses a drug and a certain type of laser light to kill cancer cells. A drug that is not active until it is exposed to light is injected into a vein. The drug collects more in cancer cells than in normal cells. Fiberoptic tubes are then used to carry the laser light to the cancer cells, where the drug becomes active and kills the cells. Photodynamic therapy causes little damage to healthy tissue. It is used mainly to treat tumors on or just under the skin or in the lining of internal organs. When the tumor is in the airways, PDT is given directly to the tumor through an endoscope.

Cryosurgery is a treatment that uses an instrument to freeze and destroy abnormal tissue, such as carcinoma in situ. This type of treatment is also called cryotherapy. For tumors in the airways, cryosurgery is done through an endoscope.

Electrocautery is a treatment that uses a probe or needle heated by an electric current to destroy abnormal tissue. For tumors in the airways, electrocautery is done through an endoscope.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

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Non-Small Cell Lung Cancer Treatment (PDQ)Patient Version