Anaplastic lymphoma kinase neoepitope-presenting tumor cell (ALK-neoepitope+ cell)

Anaplastic lymphoma kinase (ALK) neoepitope-presenting tumor cells are malignant cells that display unique peptide fragments derived from mutated or rearranged ALK proteins on their surface via Major Histocompatibility Complex (MHC) molecules (Voena & Chiarle, 2016). In many cancers, such as non-small cell lung cancer (NSCLC) and anaplastic large cell lymphoma (ALCL), ALK undergoes chromosomal translocations that result in oncogenic fusion proteins like EML4-ALK or NPM-ALK. These fusion junctions or overexpressed wild-type sequences are processed into neoepitopes, which serve as highly specific targets for the immune system because they are absent or minimally expressed in most normal adult tissues (Passoni et al., 2002). Therapeutic strategies targeting these cells include peptide or DNA vaccines (e.g., ALK-VAC) and TCR-engineered T cells (TCR-T) designed to recognize the specific peptide-MHC complex (Chiarle et al., 2008). By focusing on these neoepitopes, clinicians aim to induce a potent and selective T-cell mediated anti-tumor response that can overcome resistance to traditional small-molecule ALK tyrosine kinase inhibitors (TKIs). This approach is particularly relevant for patients who have developed resistance mutations to first- and second-generation TKIs, as the neoepitope presentation remains a viable target for immunotherapy (Russo et al., 2018).

Other names

ALK-positive tumor cellALK-derived neoantigen-presenting cellALK-fusion-positive tumor cellALK-peptide-MHC complex-bearing cell

Induction of a cytotoxic T-lymphocyte (CTL) response or direct antibody-mediated targeting against specific ALK-derived peptide fragments presented by Major Histocompatibility Complex (MHC) Class I molecules on the tumor cell surface.