Patient-specific tumor-associated antigen peptide–major histocompatibility complex (pTAA-pMHC) (pTAA-pMHC)

Patient-specific tumor-associated antigen peptide–major histocompatibility complex (pMHC) represents a personalized class of therapeutic targets in oncology [1.5.1]. These complexes consist of a short peptide fragment, derived from a tumor-specific mutation (neoantigen) or an overexpressed tumor-associated antigen, bound within the groove of a patient's specific major histocompatibility complex (MHC) molecule [1.1.4, 1.3.5]. The primary biological function of these complexes is to present intracellular protein fragments on the cell surface for surveillance by T-cells [1.2.1, 1.4.1]. In the context of cancer, these pMHCs serve as flags that allow the immune system to distinguish malignant cells from healthy tissue [1.3.3, 1.5.5]. Therapeutic strategies targeting these complexes include personalized cancer vaccines, such as mRNA-4157 and BNT122, which prime the immune system to recognize specific pMHCs [1.5.3]. Additionally, TCR-engineered T-cell (TCR-T) therapies provide T-cells with receptors specifically tuned to recognize these targets [1.2.3]. Because these targets are often unique to an individual's tumor genome, they offer high specificity and a reduced risk of systemic toxicity compared to traditional therapies [1.5.1, 1.5.5]. However, challenges remain, such as the potential for tumor immune evasion through the downregulation of MHC molecules or the loss of the target antigen [1.1.1, 1.3.5]. Furthermore, the low affinity of some TCR-pMHC interactions can lead to cross-reactivity with self-peptides, posing a risk of autoimmunity [1.1.4, 1.2.2]. Despite these challenges, targeting patient-specific pMHCs remains a cornerstone of precision immunotherapy [1.5.1].

Other names

Neoantigen-MHC complexTumor-specific antigen-MHC complexTSA-MHCpMHC complexPersonalized pMHCTumor-associated antigen-HLA complex

Recognition by T-cell receptors (TCRs) to trigger cytotoxic T-lymphocyte (CTL) mediated lysis of tumor cells.