Tumor-associated peptide antigens presented on Human Leukocyte Antigen class I (pMHC-I)

Tumor-associated peptide antigens (TAPAs) presented on Human Leukocyte Antigen (HLA) class I molecules are short protein fragments, typically 8 to 11 amino acids in length, derived from intracellular proteins and displayed on the cell surface for recognition by CD8+ T cells (Nature Reviews Cancer, 2019). These antigens can be classified into several categories, including neoantigens derived from somatic mutations, cancer-testis antigens expressed only in tumors and germ cells, and overexpressed self-antigens (Nature Reviews Immunology, 2020). In oncology, the peptide-HLA (pMHC) complex serves as a highly specific therapeutic target, allowing the immune system to distinguish malignant cells from healthy ones based on their internal proteome (Frontiers in Immunology, 2021). Modern immunotherapies, such as T-cell receptor (TCR) engineered T cells and bispecific T-cell engagers like Tebentafusp, are designed to bind these complexes with high affinity to trigger potent anti-tumor immune responses (NEJM, 2021). However, therapeutic success is often challenged by the heterogeneity of antigen expression and the ability of tumors to downregulate HLA molecules to evade immune detection (Journal for ImmunoTherapy of Cancer, 2020). Furthermore, ensuring the safety of these therapies requires rigorous screening to prevent cross-reactivity with similar peptides presented on normal tissues (Science Translational Medicine, 2013).

Other names

Tumor-associated antigens (TAAs)NeoantigenspMHC complexesHLA-restricted tumor antigensCancer-testis antigens (CTAs)Tumor-specific antigens (TSAs)

Recognition by T-cell receptors (TCRs) or TCR-mimetic antibodies, leading to the activation of cytotoxic T lymphocytes (CTLs) and subsequent lysis of the target tumor cell.