Patient-specific tumor neoantigen–derived peptide–Major Histocompatibility Complex (pMHC) on dendritic cells (Neoantigen-pMHC on DCs)

Patient-specific tumor neoantigen–derived peptide–MHC complexes on dendritic cells are the fundamental units of recognition for the adaptive immune system in personalized oncology (Sahin et al., Nature, 2017). These complexes consist of neoantigens—peptides derived from somatic mutations unique to a patient's tumor—bound to Major Histocompatibility Complex (MHC) molecules on the surface of professional antigen-presenting cells like dendritic cells (Hu et al., Nature Reviews Immunology, 2021). Their primary biological function is to present these 'non-self' signals to naive T cells, thereby priming a targeted immune response against malignant cells (Ott et al., Nature, 2017). In therapeutic applications, such as personalized neoantigen vaccines, these complexes are utilized to expand the repertoire of tumor-infiltrating lymphocytes (TILs) and overcome immune tolerance (Blass & Ott, Nature Reviews Clinical Oncology, 2021). By focusing on mutations absent from healthy tissue, drugs targeting these complexes aim to minimize off-target toxicity while maximizing anti-tumor efficacy (NCI, 2023). This approach is currently being evaluated in various solid tumors, including melanoma and lung cancer, often in combination with checkpoint inhibitors to enhance the durability of the immune response (Moderna, 2024).

Other names

Personalized neoantigen-MHC complexesTumor-specific neoepitope-HLA complexesNeoantigen-presenting dendritic cellspMHC complexesTSA-MHC complexes

The mechanism involves the interaction between the neoantigen-pMHC complex and the T-cell receptor (TCR). Dendritic cells present the neoantigen via MHC Class I to CD8+ T cells and MHC Class II to CD4+ T cells, leading to the activation, proliferation, and differentiation of these cells into effector T cells that can specifically recognize and lyse tumor cells expressing the same neoantigen (Nature Reviews Cancer, 2021; Sahin et al., Nature, 2017).