Kinetochore protein NDC80 peptide ALNEQIARL-HLA-A*02 complex (NDC80-HLA-A*02)

The ALNEQIARL peptide from NDC80 presented by HLA-A*02 is a specific peptide-major histocompatibility complex (pMHC) target used in advanced cancer immunotherapy. The parent protein, NDC80 (also known as HEC1, Highly Expressed in Cancer 1), is a critical component of the outer kinetochore required for stable microtubule-kinetochore attachment and proper chromosome segregation during mitosis (UniProt: O14777). While NDC80 is essential for cell division and is minimally expressed in most normal adult tissues, it is significantly upregulated in a wide variety of solid tumors, making it a viable tumor-associated antigen (Nakatsugawa et al., 2016, Scientific Reports). The ALNEQIARL epitope corresponds to residues 358-366 of the NDC80 protein and is specifically presented by the HLA-A*02:01 allele to CD8+ cytotoxic T lymphocytes. Therapeutic approaches targeting this complex primarily involve the development of T-cell receptor (TCR) engineered T-cell therapies designed to recognize and eliminate cancer cells presenting this specific epitope. Because NDC80 expression is strongly correlated with high proliferation rates in cancer, targeting this pMHC complex offers a strategy to selectively hit aggressive tumor cell populations while potentially sparing quiescent healthy cells.

Other names

ALNEQIARL-HLA-A*02:01HEC1 peptide-HLA-A2 complexNDC80(358-366) epitopeHighly expressed in cancer protein 1 peptide-MHC complexNDC80-A2

T-cell redirection and activation leading to targeted cytotoxicity of HLA-A*02 positive tumor cells expressing NDC80.