Patient-specific tumor-associated antigen peptide–Major Histocompatibility Complex (pMHC)

Patient-specific tumor-associated antigen peptide–Major Histocompatibility Complex (pMHC) refers to the presentation of intracellular tumor-derived proteins on the cell surface for recognition by the immune system. These complexes are formed when peptides, often derived from unique somatic mutations (neoantigens) or overexpressed proteins within a patient's tumor, are processed and loaded onto Human Leukocyte Antigen (HLA) molecules (PubMed, 2023). In the context of lifileucel (Amtagvi), the therapy utilizes the patient's own tumor-infiltrating lymphocytes (TILs) which naturally possess T-cell receptors (TCRs) evolved to recognize these specific pMHC targets. Upon reinfusion, these TILs identify the pMHC complexes on malignant cells, triggering a polyclonal cytotoxic immune response (NCI, 2024). This target is highly individualized, as the specific peptide sequences and HLA alleles vary from patient to patient. Lifileucel is the first cellular therapy approved to target these complexes for the treatment of advanced melanoma (FDA, 2024).

Other names

Tumor-associated antigen peptide-MHC complexNeoantigen-MHC complexTumor-specific antigen peptide-MHC complexpMHC complexHLA-antigen complex

Lifileucel consists of autologous tumor-infiltrating lymphocytes (TILs) that express a polyclonal repertoire of T-cell receptors (TCRs). These TCRs specifically bind to patient-specific tumor-associated antigen peptides presented by Major Histocompatibility Complex (MHC) molecules on the surface of tumor cells, leading to T-cell activation, cytokine release, and subsequent lysis of the cancer cells (FDA, 2024; Iovance Biotherapeutics, 2024).