Tumor-associated peptide-HLA complex (pHLA)

Tumor-associated peptide-HLA (pHLA) complexes are the primary targets for T-cell-based immunotherapies, consisting of short peptides derived from intracellular or surface proteins presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (NIH, 2022). In hematological malignancies such as leukemia and multiple myeloma, these complexes are identified from malignant marrow-infiltrating cells using mass spectrometry-based immunopeptidomics to delineate a 'ligandome' of tumor-exclusive or over-presented antigens (Walz et al., Blood 2022; Heidenreich et al., Blood 2018). Therapeutic strategies targeting these complexes include peptide vaccines, adoptive T-cell therapies such as TCR-T cells, and bispecific T-cell engagers known as TCERs (Immatics, 2024). These therapies aim to harness the specificity of the T-cell receptor (TCR) to recognize and eliminate cancer cells while sparing healthy tissues. However, challenges include the high degree of HLA polymorphism, potential off-target cross-reactivity with similar self-peptides, and tumor immune evasion through HLA downregulation (ResearchGate, 2023).

Other names

pMHC complexTumor-associated peptideTUMAPLeukemia-associated peptideLiTAPHLA ligandomePeptide-MHC complexTumor-/leukemia-associated peptide-HLA complexes

T-cell receptor (TCR) mediated recognition and cytotoxic T-cell activation