Phase I clinical trials show that TCR-T cells targeting MAGE-A4 are expected to treat multiple solid tumors

Of the 38 patients who received this treatment, ADP-A2M4 T cells resulted in an overall response (OR) or tumor reduction in 9 people (23.7%) and 18 (47.4%) in stable conditionLead researcher DrDavid Hong, a professor of research cancer treatment, shared the data on the clinical trial in an oral report at the 2020 annual meeting of the American Society of Clinical Oncology"So far, we haven't seen a strong response to the treatment of solid tumors with existing cell therapies, in large part because the expression of antigens is not limited to tumors,"Hong saidIn this clinical trial, I was encouraged to see lasting reactions in some patients, and these results suggest that this emerging technology based on TCR-T cells has potential in treating solid tumors"
secondary cell therapy is a form of immunotherapy that involves genetic modification of immune cells to more effectively initiate an immune response to cancerFor ADP-A2M4, T cells are isolated from patients and genetically modified to express TCR targeted at MAGE-A4, a protein that is usually expressed only in the testicles but presents in certain cancersunlike T-cells (CAR-T), which target the surface proteins of cancer cells by expressing chimeric antigen receptors (CAR), TCR-T cell therapy can target proteins commonly found inside cells by identifying fragments of proteins bound to immuno-related proteins located on the cell surfacethis Phase I clinical trial was designed as a dose-increasing study to assess the safety, tolerance, and antitumor activity of ADP-A2M4 in patients with advanced solid tumors expressed with the MAGE-A4 proteinPatients participating in this clinical trial included patients with caroblastoma, ovarian cancer, head and neck cancer, stomach cancer, vanity/round cell fat sarcoma, non-small cell lung cancer, bladder cancer, esophageal cancer, and melanomaThe participants had previously received an average of three systemic therapiesthis TCR-T cell therapy has received strong responses in specific patient groups involved in this clinical trialThe overall response rate was 43.8% for patients with caricomosarcoma and more than 90% for disease controlAfter the data cut off, there was another patient who did not confirm the reactionThe median response time in these patients was 28 weeks, and the median progression-free survival was 20 weeks Patients with lung and head and neck cancers also experienced confirmed reactions most patients (97.4%) experienced some treatment-related adverse events, the most common being low blood cell counts (lymphocyte reduction, white blood cell reduction, neucutane cell reduction, anemia and platelet reduction) Half of the patients develop cytokine release syndrome Two patients developed clinical trial-related deaths, which led to changes to the lymphocyte removal program and eligibility criteria "The side effects observed in this clinical trial are broadly consistent with those experienced in cancer patients who received chemotherapy and cell therapy to remove lymphocytes," Hong said This study is a good proof of concept for the treatment of solid tumors and suggests that cell therapy may play a role in these indications the study as part of an ongoing strategic alliance between the University of Texas MD Anderson Cancer Center and Adaptimmune to accelerate the development of new T-cell therapies for multiple types of cancer Conversion research and analysis of related biomarkers continues These findings led to a low-dose branch study of radiation, ADP-A2M4 phase II clinical trials in sarcoma, and AStage I clinical trials of The next generation of T-cell therapy targeted by Adaptimmune to MAGE-A4 --- ADP-A2M4CD8 ---.