Patient-specific neoantigen–Major Histocompatibility Complex and tumor-specific T-cell receptor (Neoantigen-MHC/TCR complex)

The patient-specific neoantigen–Major Histocompatibility Complex (MHC) and its corresponding tumor-specific T-cell receptor (TCR) represent the fundamental unit of personalized cancer immunotherapy. Neoantigens are novel peptides derived from somatic mutations unique to an individual's tumor, which are processed and presented on the cell surface by MHC molecules, known as Human Leukocyte Antigens (HLA) in humans [1, 7]. Because these neoantigens are absent in healthy tissues, they are recognized as "non-self" by the immune system, allowing for highly specific targeting that bypasses central thymic tolerance [7, 12]. Therapeutic strategies targeting this complex include the adoptive transfer of T-cells engineered with patient-specific TCRs (TCR-T therapy) and personalized neoantigen vaccines designed to expand endogenous T-cell populations [2, 6]. This approach is particularly promising for solid tumors where traditional CAR-T therapies face challenges due to the lack of suitable surface antigens [1, 13]. However, the high degree of personalization requires complex bioinformatic prediction, HLA typing, and individualized manufacturing processes to ensure the TCR accurately recognizes the specific peptide-MHC complex [2, 8].

Other names

Neoantigen-HLA complexTumor-specific TCRPersonalized neoantigen-MHCNeoepitope-MHC complexpMHC-TCR complexPrivate neoantigen-TCR axis

Adoptive cell transfer of T-cells engineered with patient-specific T-cell receptors (TCR-T) to recognize neoantigens, or induction of endogenous T-cell responses via personalized neoantigen vaccines that present these complexes to the immune system.