PERSONALISED T cell activation induced strong and durable immune responses with an acceptable safety profile in patients with chronic lymphocytic leukaemia receiving Bruton’s tyrosine kinase inhibitor-based therapy, according to results from a phase one clinical trial.
Rationale for Personalised T Cell Therapy
Chronic lymphocytic leukaemia remains largely incurable, despite major advances with Bruton’s tyrosine kinase inhibitor-based regimens. Therapeutic activation of tumour specific T cells represents a potential strategy for achieving long term disease control, but its clinical application has been limited by the complexity of personalised drug development and a lack of suitable mutation derived neoepitopes. Investigators therefore evaluated iTAC-XS15-CLL01, a personalised warehouse based multipeptide T cell activator combined with the Toll like receptor one two ligand XS15, designed to stimulate chronic lymphocytic leukaemia specific immune responses.
Study Design and Safety Outcomes
This open label, single centre, phase one study enrolled adults with chronic lymphocytic leukaemia in Germany who had achieved at least partial remission with residual disease following six–eight months of Bruton’s tyrosine kinase inhibitor-based therapy. Participants received three monthly subcutaneous injections of iTAC-XS15-CLL01, consisting of eight chronic lymphocytic leukaemia specific peptides selected according to individual HLA allotyping, combined with XS15.
Twenty patients entered the treatment phase and were followed for six months. The median age was 56.5 years, and all participants were White. Treatment was generally well tolerated, with no grade four adverse events, treatment related serious adverse events, or deaths reported. The most frequent grade three adverse events were injection site erythema, granuloma, and ulceration, all of which were local reactions.
Immunogenicity and Clinical Implications
Robust T cell responses were induced in 19 of 20 patients by the end of treatment, targeting multiple peptides. These immune responses persisted at six months follow up in 16 of 19 evaluable patients, with increasing response intensity observed through the end of the study period. The findings demonstrate that personalised multipeptide T cell activation is feasible in chronic lymphocytic leukaemia and can generate sustained immune responses even in patients receiving ongoing targeted therapy.
The authors conclude that iTAC-XS15-CLL01 shows potential as a novel immunotherapeutic strategy in chronic lymphocytic leukaemia and warrants further investigation in phase two clinical trials to better define its efficacy and long-term clinical benefit.
Reference
Heitmann JS et al. Personalised multipeptide-based T-cell activator for chronic lymphocytic leukaemia: an open-label, single-centre, phase 1 study. Lancet Hematology. 2026;13(2):E74-85.
