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20 years of changes in the clinical development of T cell adoptive therapy
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20 years of changes in the clinical development of T cell adoptive therapy.
Chimeric antigen receptor and T cell receptor (CAR-T/TCR-T) cellular immunotherapy is a targeted cell therapy that uses the cytotoxic potential of T cells to eradicate cancer cells in an antigen-specific manner.
The treatment method firstly genetically modifies the T cells isolated from the patient to express the required CAR or TCR on the cell surface. The genetically modified T cells are then injected into the patient’s body, and eventually come into direct contact with the cancer antigen to kill the cancer cells.
In the past 20 years, CAR-T and TCR-T cell therapies have undergone earth-shaking changes from conceptual verification trials to thousands of registered clinical trials.
In 2017, the US Food and Drug Administration (FDA) approved two CAR-T therapies for the first time, namely tisagenlecleucel (Kymriah®) and Axicabatagene ciloleucel (Yescarta®), for the treatment of acute lymphoblastic leukemia and diffuse large B cell respectively Lymphoma.
So far, 5 CAR-T therapies have been approved. CAR-T/TCR-T therapy, as a revolutionary biotechnological product in cancer treatment, demonstrates the outstanding potential of conquering cancer in the future.
In the past 20 years, there have been thousands of registered clinical trials on clinical trials, of which 627 are active. Of these active clinical trials, 390 trials (40.7%) are in phase 1, 221 trials (23.1%) are in phase 1/2 or phase 2, and 10 are in phase 2/3 or phase 3. .
Beginning in 2007, the clinical trials of CAR-T/TCR-T cell therapy began to grow slowly. From 2013 to 2020, cellular immunotherapy has experienced rapid and accelerated growth.
Although the number of start-up trials for all therapies has increased, the number of CAR-T trials has grown significantly faster. From 2013 to the end of 2020, the start-up compound annual growth rate of CAR-T trials was 38.7%, while my other therapies Is 25.6%.
In addition to CD19, the most common clinical targets for CAR-T therapy also include BCMA, CD22, etc. The number of BCMA trials has increased from 7 trials in 2016 to 85 in 2020, and has achieved significant results in trials for the treatment of multiple myeloma. Encouraging results.
Before 2015, trials for solid tumors were almost synchronized with trials for hematological tumors, but in 2016-2020, 479 (64%) trials for hematological tumors were launched, and 265 trials for solid tumors were launched . One factor contributing to the overall increase in hematology trials is the increase in the number of trials initiated by China.
In 2016-2020, trials initiated for hematological tumors far exceeded those for solid tumors. Most hematology tests (90%) were for CAR-T or multiple myeloma for B-cell leukemia and lymphoma. Other blood tumor tests are for myeloid leukemia or T-cell lymphoma and Hodgkin’s lymphoma. Although it is mainly CAR therapy, it also includes TCR therapy and other related therapies.
Since 2013, the number of CAR-T/TCR-T clinical trials recruiting patients with different solid tumors has increased rapidly. Targets for solid tumors include more than 60 antigens or oncoproteins. The most common target antigens are NY-ESO-1, mesothelin, EGFRvIII, GD2, HER2 and MUC1. The most common target tissue types are brain and nerve tissue cancer (52 items), liver cancer (42 items), female reproductive system cancer (37 items), and lung cancer (31 items).
The analysis of clinical trials shows that in the past 20 years, CAR-T/TCR-T cellular immunotherapy has experienced rapid development. In addition to CD19, more target options make CAR-T therapies more diverse.
Some new therapies have also been developed. For example, some clinical trials use bispecific CAR-T cells (NCT03271515, NCT03241940) that simultaneously target CD19 and CD20 or CD22; express recombinant receptors, such as EGFRt, for antibody-mediated Patients with CAR-T cells are eliminated, or PD-1 deleted T cells are used to avoid immunosuppression (NCT03085173, NCT03298828).
In addition, the combined use of anti-CD19 and anti-BCMA CAR-T cells has an overall response rate of 95%. These CAR-T/TCR-T clinical trials represent the future trend of cellular immunotherapy.
At present, CAR-T cell therapy still has many obstacles to solid tumors, but as more and more CAR-T/TCR-T products carry out clinical trials, I believe we can see CAR-T/TCR-T soon Mutation progression in solid tumors.
1.Tracking the CAR-T Revolution: Analysis of Clinical Trials of CAR-T and TCR-T Therapies for the Treatment of Cancer (1997–2020). Healthcare (Basel). 2021 Aug; 9(8): 1062.
(source:internet, reference only)