Adaptimmune’s Afami-cel is the first FDA-approved T-cell receptor therapy for synovial sarcoma

1. Afami-cel (Tecelra) is the first genetically engineered T-cell receptor therapy for synovial sarcoma
2. Afami-cel demonstrated an overall response rate of 39% in synovial sarcoma patients.

The Latest

SPEARHEAD-1, an open-label, non-randomized, phase 2 clinical trial funded by Adaptimmune, evaluated Afamitresgene autoleucel (Afami-cel or Tecelra) in 44 patients with MAGE-A4+ advanced synovial sarcoma, who had already undergone chemotherapy. Afami-cel achieved an overall response rate of 39% in patients with advanced synovial sarcoma, and a median survival of 15.4 months.

Physician’s Perspective

Synovial sarcoma is a rare and aggressive cancer that originates in soft tissue and bone. One-third of synovial sarcoma diagnoses occur in adults under 30. The 5-year survival rate for adults is between 50-60%. Synovial sarcoma often arises from a chromosomal translocation, where DNA from one chromosome is swapped to a new location. This abnormal new arrangement causes expression of proteins that promote uncontrolled cell growth and tumor development. Existing treatment options for synovial sarcoma include surgical resection, and radio-chemotherapy. Despite these treatments, synovial carcinoma often persists or recurs. Afami-cel is a novel treatment approved for synovial sarcoma which aims to use the patient’s own immune system to fight cancer cells. This comes in a line of novel immunotherapy agents changing the landscape in cancer treatment.

Molecular Targets

MAGE-A4 is a protein that can be found on synovial sarcoma cells. These are referred to as MAGE-A4+ synovial sarcoma cells. Afami-cel works by reprogramming a patient’s immune cells, called T cells, to better recognize the MAGE-A4 protein on cancer cells and target these cells for destruction. Afami-cel does this by introducing genetically engineered material into T cells so that they express surface receptors with a very high affinity (or attraction) for MAGE-A4+ cancer cells.

Company History

Adaptimmune is a biopharmaceutical company specializing in the treatment of cancer with novel immunotherapy agents. Presently, Adaptimmune is also developing a MAGE-A4 TCR therapy called uza-cel, which is currently in phase 2 clinical trials for treatment of ovarian cancer. Uza-cel may also be evaluated in the treatment of head and neck cancer.

Further reading: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00319-2