William G. Wierda, M.D., Ph.D. University of Texas MD Anderson Cancer Center

IMMUNOLOGY

Immunotherapy with ISF35-Transduced Autologous CLL B-Cells

Grant awarded in 2004

Abstract:

Chronic lymphocytic leukemia (CLL) is currently considered incurable with standard treatments. We can now achieve complete remission in the majority of chemotherapy naïve patients; however, their leukemia will likely eventually return. In order to advance therapy for patients with CLL, new treatments that work through complimentary mechanism to chemotherapy are needed.

Recruiting the immune system to react against leukemia cells is one such treatment modality. A strategy has been developed whereby patients' leukemia cells are treated with a virus that causes them to produce a protein called ISF35. Production of ISF35 by the leukemia cells stimulates the patients' immune system to recognize and react against the leukemia. The treated cells are administered to patients as a vaccine. The virus does not reproduce and therefore is of little risk for infection to patients. Preliminary work aimed at assessing the tolerability of this treatment in which patients received a single dose of cells treated with ISF35 showed not only that this treatment can safely be given and was well tolerated, but also showed indications of therapeutic benefit such as reduction in leukemia cell counts, lymph node size, and spleen size.

The next step in developing this therapy into treatment for patients with CLL, and the goal of this proposal, is to administer repeated doses and evaluate patients for therapeutic response. This proposal will also evaluate immune function of treated patients to confirm that the treatment is working by the proposed mechanism and in order to optimize effectiveness of the therapy. This will provide an important and novel therapeutic modality to advance treatment of patients with CLL and potentially other malignancies.