Immunopeptidome-guided personalized peptide vaccines induce potent T cell response in chronic lymphocytic leukemia

T cell immunity is central for the control of malignant disease. Chronic lymphocytic leukemia (CLL) lacks mutation-derived T cell neoantigens, yet harbours frequent tumor-associated antigens as targets for therapeutic vaccine design. iVAC-XS15-CLL01 is a warehouse-based personalized muli-peptide vaccine of immunopeptidome-defined CLL-associated antigens. We report the results of an open-label phase I trial evaluating the safety, immunogenicity and first efficacy of iVAC-XS15-CLL01 in 20 CLL patients who achieved partial remission under bruton’s tyrosine kinase inhibitor treatment. Vaccination was well tolerated and induced potent T cell response in 95% of patients, targeting multiple vaccine peptides. CLL-specific T cell responses were mediated by polyfunctional T helper 1 CD4+ and CD8+ T cells and persisted until 6 month follow up. Minimal residual disease reduction (median 50%) was observed in 90% of patients and correlated with vaccine-induced T cell response, providing first evidence of iVAC-XS15-CLL01’s clinical efficacy, warranting its further evaluation in an upcoming phase II trial.