Patient-specific tumor-associated and neoantigen peptides presented on Major Histocompatibility Complex (pMHC)

Patient-specific tumor-associated and neoantigen peptides presented on the Major Histocompatibility Complex (MHC) are a diverse class of targets central to personalized cancer immunotherapy. These peptides are derived from intracellular proteins—either mutated (neoantigens) or aberrantly expressed (tumor-associated antigens)—that are processed and displayed on the cell surface by MHC molecules for recognition by T cells (Schumacher & Schreiber, 2015, Science). This presentation serves as the primary mechanism by which the adaptive immune system identifies and eliminates malignant cells. In many cancers, the landscape of these peptides is unique to the individual patient, providing a highly specific target for therapeutic intervention (Hacohen et al., 2017, Nature). Drugs interacting with these targets include personalized vaccines, such as mRNA-4157 or Autogene cevumeran, which aim to prime the patient's immune system to recognize these specific signatures (Weber et al., 2024, Lancet; Rojas et al., 2023, Nature). Additionally, adoptive cell therapies like TCR-engineered T cells and bispecific T-cell engagers like Tebentafusp are designed to bind directly to these peptide-MHC complexes to induce tumor cell lysis (Nathan et al., 2021, NEJM). However, therapeutic success is often challenged by tumor-mediated immune evasion, such as the loss of HLA expression or the development of antigen-negative clones (Sahin & Türeci, 2018, Science).

Other names

Tumor-specific antigensNeoantigensTumor-associated antigensHLA-peptide complexesCancer-testis antigensTSAsTAAs

Induction of de novo or expansion of existing antigen-specific T-cell responses (vaccines) or direct targeting of the peptide-MHC complex by engineered receptors (TCR-T, bispecifics) to trigger cytotoxic T-lymphocyte mediated lysis of tumor cells (Schumacher & Schreiber, 2015, Science).