An antileukaemia vaccine can overcome tolerance and generate immune responses in leukaemia patients  

 

 

Based on preclinical studies in mice, we generated patient-derived antileukaemia vaccines expressing the human costimulatory molecules CD40 ligand and interleukin 2 (IL-2) using autologous blasts and genetically engineered syngeneic skin fibroblasts. All 10 patients were in complete remission and were off immunosuppressive drugs. Patients received up to six subcutaneous injections of the vaccine, and no serious side effects or adverse events were seen. Frequencies of major histocompatibility complex T cells reactive against the patient’s own blasts increased 10- to 890-fold, the researchers found, and these tumor-specific cells included Th1 and Th2 types. The increase lasted for up to three months after the final immunization. In two of the patients, IgG antibodies that bound to their tumor blasts were identified. While none of the patients were taking immunosuppressive drugs, none of them developed graft versus host disease with immunization. 

Albeit this phase 1 setting is not appropriate to evaluate long-term outcome, it is somehow encouraging to observe that eight of the ten patients survived disease-free for up to 62 months post-treatment. Although the results are consistent with a therapeutic benefit, any estimate of the vaccine’s true value will require more rigorous testing in a randomized trial.  

 

Bibliographical reference:

Rousseau RF et al.: "Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation", Blood. 2006 Feb 15;107(4):1332-41

 

Raphael F. Rousseau
Pediatric Oncology, Centre Leon Berard, Lyon, France