The results are encouraging

Adoptive T-cell therapy of ADP-A2M4 with expression of the T-cell receptor (TCR) directed against the MAGE-A4 antigen has shown efficacy in patients with various types of solid tumors, including synovial sarcoma, head and neck cancer, lung cancer. The study was conducted by the staff of the Anderson Cancer Center at the University of Texas, the results were presented in an oral report at the annual meeting of the American Society of Clinical Oncology in 2020.

Among 38 patients treated, ADP-A2M4 T cells resulted in tumor reduction in 9 patients (23.7%) and stabilization of the disease in 18 patients (47.4%).

Adoptive cell therapy is a form of immunotherapy in which a patient's T–lymphocytes are modified to increase their activity against cancer. In this study, T cells were forced to express TCR targeting the MAGE-A4 protein, usually expressed only in the testis, but present in certain cancers.

Unlike CAR T therapy, in which T cells target the surface proteins of cancer cells, TCR T cell therapy allows immune cells to bind to proteins normally found inside the cancer cell.

Phase I of the clinical trial was organized to select the dose and evaluate the safety, tolerability and antitumor activity of ADP-A2M4 in patients with solid tumors with MAGE-A4 protein expression. The study included patients with synovial sarcoma, ovarian cancer, head and neck cancer, stomach cancer, myxoid and round-cell liposarcoma, non-small cell lung cancer, bladder cancer, esophageal cancer and melanoma.

The effectiveness of therapy differed in the groups of patients in the study. In synovial sarcoma, the overall response rate was 43.8%, and the level of disease control was more than 90%. There was also an additional patient with an unconfirmed response after the termination of the study. The average response time in these patients was 28 weeks, and the average time without disease progression was 20 weeks. Confirmed responses were also noted in patients with lung cancer and head and neck cancer.

The majority of patients (97.4%) had side effects of treatment, the most common of which were from the hematopoiesis (lymphopenia, leukopenia, neutropenia, anemia and thrombocytopenia). Half of the patients experienced cytokine release syndrome. During the study, two patients died, which prompted a change in the mode of lymphodepletion (elimination of cells capable of destroying modified T-lymphocytes) and acceptance criteria.

However, as the authors write, the side effects observed in the study were largely consistent with the side effects that cancer patients who receive chemotherapy and cell therapy usually experience.

This study is a confirmation of the concept of solid tumor treatment and proves that cell therapy can play an important role in this in the future.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of MD Anderson Cancer Center: Adaptive T-cell therapy ADP-A2M4 targeting MAGE-A4 shows early activity in patients with advanced solid tumors.