An autologous vaccine expressing transgenic human CD40L and IL-2 provides immunotherapy of high-risk acute leukemia

06-26-2006

According to recent research published in the journal Blood, "CD40L generates immune responses in leukemia-bearing mice, an effect that is potentiated by IL-2. We studied the feasibility, safety, and immunologic efficacy of an IL-2- and CD40L-expressing recipient-derived tumor vaccine consisting of leukemic blasts admixed with skin fibroblasts transduced with adenoviral vectors encoding human IL-2 (hIL-2) and hCD40L."

"Ten patients (including seven children) with high-risk acute myeloid (n=4) or lymphoblastic (n=6) leukemia in cytologic remission (after allogeneic stem cell transplantation [n=9] or chemotherapy alone [n=1]) received up to six subcutaneous injections of the IL-2/CD40L vaccine," said Raphael F. Rousseau and colleagues at Baylor College of Medicine. "None of the patients were receiving immunosuppressive drugs. No severe adverse reactions were noted. Immunization produced a 10- to 890-fold increase in the frequencies of major histocompatibility complex (MHC)-restricted T cells reactive against recipient-derived blasts."

"These leukemia-reactive T cells included both T-cytotoxic/T-helper 1 (Th1) and Th2 subclasses, as determined from their production of granzyme B, IFN-gamma, and IL-5," stated the scientists. "Two patients produced systemic IgG antibodies that bound to their blasts. Eight patients remained disease free for 27 to 62 months after treatment (five-year overall survival, 90%). Thus, even in heavily treated patients, including recipients of allogeneic stem cell transplants, recipient-derived antileukemia vaccines can induce immune responses reactive against leukemic blasts. This approach may be worthy of further study, particularly in patients with a high risk of relapse."

Rousseau and associates published their study in Blood (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;107(4):1332-1341).

For additional information, contact Raphael F. Rousseau, Texas Children's Cancer Center, Center for Cell and Gene Therapy, Baylor College of Medicine, Methodist Hospital, Houston, TX 77030, USA. rfrousse@texaschildrenshospital.org.

This article was prepared by Cancer Vaccine Week editors from staff and other reports. Copyright 2006, Cancer Vaccine Week via NewsRx.com.