Stadler, Serena and Blasco, Rafael B. and Singh, Vijay Kumar and Damm-Welk, Christine and Ben-Hamza, Amin and Welters, Carlotta and Hansmann, Leo and Chiarle, Roberto and Woessmann, Wilhelm (2025) Endogenous CD4+ T Cells That Recognize ALK and the NPM1::ALK Fusion Protein Can Be Expanded from Human Peripheral Blood. CANCER IMMUNOLOGY RESEARCH, 13 (4). pp. 487-495. ISSN 2326-6066, 2326-6074
Full text not available from this repository. (Request a copy)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 ALK-specific CD4+ T cells. We screened peripheral blood of 10 patients with ALK-positive anaplastic large-cell lymphoma in remission and six healthy donors for CD4+ T-cell responses to the whole ALK fusion protein, nucleophosmin 1 (NPM1)::ALK. ALK-specific CD4+ T cells were detected in 15 individuals after stimulation with autologous dendritic cells pulsed with long-overlapping ALK peptide pools. CD4+ T-cell epitopes were predominantly located within three specific regions (p102-188, p257-356, and p593-680) in the ALK portion of the fusion protein. We detected CD4+ T cells in one patient that recognized the NPM1::ALK fusion neoepitope and identified a corresponding T-cell receptor (TCR) by TCR alpha beta single-cell sequencing. The NPM1::ALK fusion-specific TCR was HLA-DR13-restricted and conferred antigen specificity when expressed in a TCR- reporter cell line (58 alpha-beta-). Together, our data provide evidence of ALK-specific CD4+ T cells in human peripheral blood, describe target epitopes in patients, and support the consideration of CD4+ T cells in the development of ALK-specific immunotherapies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANAPLASTIC LYMPHOMA KINASE; IMMUNE-RESPONSE; TYROSINE KINASE; TARGET ANTIGENS; TUMOR-ANTIGEN; IDENTIFICATION; ONCOANTIGEN; NEOANTIGENS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 May 2026 05:42 |
| Last Modified: | 19 May 2026 05:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67475 |
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