Personalised multipeptide-based T-cell activator for chronic lymphocytic leukaemia: an open-label, single-centre,...

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Therapeutic T-cell activation offers potential for sustained cancer control but faces challenges in personalized drug design and neoepitope availability.
• Chronic lymphocytic leukemia (CLL) treatment often involves Bruton's tyrosine kinase inhibitors (BTKi).

Purpose of the Study:

• To evaluate the immunogenicity, safety, and toxicity of iTAC-XS15-CLL01, a personalized multipeptide T-cell activator combined with XS15.
• To assess the efficacy of this combination therapy in patients with CLL undergoing BTKi-based treatment.

Main Methods:

• A Phase 1, open-label, single-center study in Germany enrolled 20 adult patients with CLL.
• Patients received three monthly subcutaneous doses of iTAC-XS15-CLL01 (peptides + XS15) after achieving partial remission on BTKi therapy.
• T-cell responses were assessed using IFNγ ELISpot assays, and adverse events were monitored.

Main Results:

• T-cell responses targeting multiple peptides were induced in 95% of patients by the end of treatment and persisted in 84% at 6-month follow-up.
• The most common grade 3 adverse events included injection-site erythema (15%), granuloma (10%), and ulceration (5%).
• No grade 4 adverse events or treatment-related deaths were reported.

Conclusions:

• iTAC-XS15-CLL01 demonstrates potential as a potent immunotherapeutic agent for chronic lymphocytic leukemia.
• Further evaluation in Phase 2 trials is recommended to confirm these findings and explore broader applications.