Anaplastic lymphoma kinase-derived peptide epitope presented on human leukocyte antigen (ALK-HLA complex)

The ALK-derived peptide epitope presented on HLA refers to specific fragments of the Anaplastic Lymphoma Kinase (ALK) protein that are processed and displayed on the cell surface by Human Leukocyte Antigen (HLA) molecules (Passoni et al., 2002, Blood). ALK is a receptor tyrosine kinase that is often mutated, rearranged, or overexpressed in various malignancies, including non-small cell lung cancer (NSCLC), neuroblastoma, and anaplastic large cell lymphoma (ALCL) (UniProt P35916). These peptide-HLA complexes serve as critical targets for the adaptive immune system, particularly CD8+ cytotoxic T cells, which recognize them via T-cell receptors (TCRs) (Passoni et al., 2006, Blood). In the context of immunotherapy, these epitopes are utilized to develop TCR-engineered T-cell (TCR-T) therapies, peptide vaccines, and TCR-mimetic antibodies designed to selectively eliminate ALK-expressing tumor cells (He et al., 2017, Journal of Hematology & Oncology). Because ALK expression is largely restricted to the developing nervous system and is minimal in healthy adult tissues, these epitopes represent highly specific targets with a potentially favorable safety profile (Singh et al., 2017, Cancers). However, therapeutic efficacy can be challenged by HLA downregulation or the emergence of escape mutations within the epitope sequence (Chiarle et al., 2008, Nature Reviews Cancer).

Other names

ALK peptide-MHC complexALK-pMHCALK-derived tumor-associated antigen epitopeALK-derived neoepitopeALK-HLA-A*02:01 complex

Recognition of the peptide-HLA complex by T-cell receptors (TCRs) or TCR-mimetic molecules, triggering cytotoxic T-lymphocyte mediated apoptosis of the target cell.