Endogenous CD4+ T Cells That Recognize ALK and the NPM1::ALK Fusion Protein Can Be Expanded from Human Peripheral Blood

• DOI: 10.1158/2326-6066.cir-24-0445
• Publication Date: 2025-01-07T15:56:38Z
• Authors: Serena Stadler; Rafael B. Blasco; Vijay Kumar Singh; Christine Damm-Welk; Amin Ben-Hamza; Carlotta Welters; Leo Hansmann; Roberto Chiarle; Wilhelm Woessmann

Abstract Anaplastic lymphoma kinase (ALK) fusion proteins resulting from chromosomal rearrangements are promising targets for cancer immunotherapy. Although ALK-specific CD8+ T cells and epitopes presented on MHC class I have been identified in patients with ALK-positive malignancies, little is known about CD4+ cells. We screened peripheral blood of 10 anaplastic large-cell remission six healthy donors T-cell responses to the whole ALK protein, nucleophosmin 1 (NPM1)::ALK. were detected 15 individuals after stimulation autologous dendritic pulsed long-overlapping peptide pools. predominantly located within three specific regions (p102-188, p257-356, p593-680) portion protein. one patient that recognized NPM1::ALK neoepitope a corresponding receptor (TCR) by TCRαβ single-cell sequencing. The fusion–specific TCR was HLA-DR13–restricted conferred antigen specificity when expressed TCR− reporter cell line (58α−β−). Together, our data provide evidence human blood, describe target patients, support consideration development immunotherapies.