Treatment procedures
The single dose cell therapy drug is prepared and administered as follows:
Step 1: Patients are screened to make sure that their synovial sarcoma expresses HLA-A*02 and MAGE-A4.
Step 2: Next, lymphodepletion conditioning (LD) is carried out. Upon completion of lymphodepletion, T cells are collected from the patient. The MAGE-A4 receptor is engineered, and the modified T cells are grown in the laboratory for expansion. T cell preparation takes 6 weeks, during which time patients receive chemotherapy.
Step 3: Patients who will undergo treatment are given immune suppressant drugs prior to the treatment with the goal of eliminating endogenous immune cells, including regulatory T cells whose presence likely interferes with the cell therapy drug.
Step 4: The affinity-enhanced T cells are returned to the same patients as a single infusion.
Outcomes, efficacy, and potentials
Clinical trials have obtained consistent outcomes of patients experiencing tumor completion remission, partial remission, or sensitivity to the cell therapy drug. Besides synovial sarcoma, tumor antigen MAGE-A4 is also found to be expressed at considerable levels in gastroesophageal cancer, melanoma, non-small cell lung cancer, ovarian cancer, squamous cell head/neck cancers, and urothelial cancer.17 The success of afami-cel in synovial sarcoma has great potential to be translated into the treatment of all of the above-described solid malignancies. There's hope in time that the exorbitant price tag of $2.2 million will be substantially reduced to make the drug more accessible to more patients.
17. Hong, D. S., Van Tine, B. A., et al. (2023). Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A*02+ patients: a phase 1 trial. Nature Medicine, 29(1), 104–114. https://doi.org/10.1038/s41591-022-02128-z
