Mutant anaplastic lymphoma kinase-derived peptide neoantigen (Mutant ALK neoantigen)

Mutant anaplastic lymphoma kinase (ALK)-derived peptide neoantigens are novel epitopes generated by somatic mutations in the ALK gene, which are subsequently processed and presented by Major Histocompatibility Complex (MHC) molecules on the surface of malignant cells (PubMed: 33649203). These neoantigens are highly tumor-specific because they arise from genetic alterations not present in normal tissues, such as the R1275Q or G1202R point mutations frequently observed in neuroblastoma and resistant non-small cell lung cancer (NSCLC) (PubMed: 18923524, 31533962). In the context of oncology, these peptides serve as critical targets for the adaptive immune system, specifically for CD8+ cytotoxic T cells that can recognize the mutant peptide-MHC complex via their T-cell receptors (TCRs). While traditional ALK inhibitors target the kinase domain's enzymatic activity, neoantigen-based therapies, including personalized vaccines and TCR-engineered T-cell (TCR-T) therapies, aim to induce a direct immune-mediated destruction of the tumor (PubMed: 33649203). These approaches are particularly relevant for overcoming resistance to tyrosine kinase inhibitors (TKIs), as they provide an alternative mechanism to eliminate cells harboring specific resistance mutations. Consequently, mutant ALK neoantigens represent a promising frontier in precision immunotherapy for ALK-driven cancers (UniProt: P29185).

Other names

ALK-derived neoepitopeMutated ALK peptideALK neoantigenAnaplastic lymphoma kinase mutant peptide

Recognition of the mutant peptide-MHC complex by T-cell receptors (TCRs), leading to the activation of cytotoxic T lymphocytes (CTLs) and subsequent lysis of tumor cells expressing the specific ALK mutation (PubMed: 33649203).