Patient-specific neoantigen and tumor-associated antigen peptide-MHC complexes (pMHC)

Patient-specific neoantigen and tumor-associated antigen (TAA) peptide-MHC (pMHC) complexes are the primary targets for cellular and vaccine-based cancer immunotherapies (Source: Nature Reviews Cancer, 2021). These complexes consist of short peptide fragments, derived from either mutated proteins (neoantigens) or overexpressed self-proteins (TAAs), presented on the cell surface by Major Histocompatibility Complex (MHC) molecules (Source: Science, 2015). In a healthy state, MHC molecules present self-peptides that the immune system ignores; however, in cancer, the presentation of non-self or aberrant peptides allows the immune system to distinguish malignant cells from healthy tissue (Source: NIH, National Cancer Institute). Therapeutic strategies targeting these complexes include personalized mRNA vaccines, such as mRNA-4157, which prime the immune system to recognize specific neoantigens, and TCR-engineered T-cell (TCR-T) therapies like Afamitresgene autoleucel (Source: Moderna; Adaptimmune). Because these targets are often highly specific to the tumor or even the individual patient, they offer a pathway toward precision oncology with potentially reduced systemic toxicity compared to traditional chemotherapy (Source: PubMed, PMID: 33024317). However, challenges remain, such as the loss of MHC expression by tumor cells as a mechanism of resistance and the risk of cross-reactivity with similar peptides found in vital organs (Source: Frontiers in Immunology, 2020).

Other names

Neoantigen-MHC complexesTumor-associated antigen-MHC complexespHLA complexesTumor-specific antigen-MHC complexespMHC complexesAntigen-HLA complexes

Recognition by T-cell receptors (TCRs) or TCR-mimetic antibodies to trigger cytotoxic T-lymphocyte-mediated destruction of tumor cells (Source: PubMed, PMID: 31434910).