Afamitresgene autoleucel

Melanoma-associated antigen A4 (MAGE-A4) is an intracellular cancer-testis antigen that is predominantly expressed by cancer cells. MAGE proteins limit tumour suppression by inhibiting p53. While MAGE-A4 expression in normal tissues is restricted, it is expressed in more than 50% of carcinomas of various cancers, including non-small-cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), gastroesophageal carcinoma, bladder carcinoma, and synovial sarcoma. MAGE-A4 is intracellularly processed into smaller peptide fragments that are co-presented with human leukocyte antigens (HLAs) on the cell surface: Together, these components are called an epitope and can be weakly recognized by low-affinity natural T cell receptors (TCRs).

Afamitresgene autoleucel is a genetically modified autologous T cell immunotherapy where a patient's own T cells are genetically modified to target the MAGE-A4 protein on cancer cells. These modified T cells are engineered to express a T cell receptor (TCR) that specifically recognizes a MAGE-A4 peptide presented by HLA-A02 on the cell surface. When the TCR binds to this peptide-HLA complex, it activates the T cells, leading to their multiplication, the release of cytokines, and the destruction of cancer cells expressing MAGE-A4/HLA-A02. This therapy shows strong effects against various cancer cells with this specific protein-HLA combination.