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| |  AACR: Vaccination with Tumor Cells Triggers Immune Response in Leukemia Patients By Brian Reid WASHINGTON, DC -- July 14, 2003 -- Transgenic skin fibroblasts secreting transgenic IL-2 and CD40L, combined with autologous leukemia blasts, prompts an immune reaction in patients with high-risk leukemia and appears to be safe, according to an early clinical stage study. The vaccination technology is designed to get around a gap in the understanding of which specific peptides may trigger an immune system reaction by reinjecting the leukemia blast cells, according to researchers led by Raphael F. Rousseau, MD, PhD, from Baylor College of Medicine, in Houston, Texas, United States. Leukemic cells generally lack the costimulatory surface molecules necessary for induction of a T-cell response and thus induce specific T-cell anergy. CD40L has been shown to up-regulate the expression of adhesion, costimulatory, and MHC molecules, therefore augmenting antigen presentation by normal and malignant B cells, and by antigen-presenting cells, Dr. Rousseau explained. Murine leukemia/lymphoma models also showed that CD40L stimulates activated CD4+ and CD8+ T cells, therefore augmenting the immune response to CD40-malignancies. This effect is potentiated by IL2 (Dilloo et al., Blood 1997;90:1927). "In those patients already in remission, we have seen quite a strong immune response," said Dr. Rousseau. "It gives us perspective in the immune response in the human." He presented the study's findings here July 12th at the 94th Annual Meeting of the American Association for Cancer Research. The researchers studied 9 patients with acute leukemia thus far, all of them considered to be at high risk for relapse, with a predicted relapse risk of more than 50% at 2 years. Seven of the patients were children, 6 had acute lymphoblastic leukemia, and 7 had received autologous bone marrow. The researchers first took the skin fibroblasts and transduced them with vectors encoding IL-2 and CD40L. That preparation was then injected subcutaneously with the leukemia blasts as many as 6 times, with 1 to 2 weeks between injections. In the 8 evaluable patients, there was 1 relapse at 22 weeks. All other patients remained disease free, with the time since the first injection ranging from 1 to 33 months. All patients were off immunosuppressive drugs. Dr. Rousseau said that clinical work will continue, and additional work will not only refine the vaccination technology but help in the search for specific antigens that could be used in future vaccination techniques.
[Study title: Treatment of High-Risk Acute Leukemia with an Autologous Vaccine-Expressing Transgenic IL-2 and CD40L. Abstract R2974]
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