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

IMMUNOLOGY

Immunotherapy with ISF35-Transduced Autologous CLL B-Cells

Update:

CLL is currently considered incurable with standard treatments. We are exploring a treatment modality where we recruit the immune system to react against and eliminate the leukemia cells.

A strategy has been developed whereby patients' leukemia cells are infected with a virus in the lab that causes them to produce a protein called ISF35. Production of ISF35 causes the immune system to recognize and react against the leukemia cells. The infected cells producing ISF35 are given as a vaccine to patients. We completed enrollment in the Phase I trial of this treatment; patients received a single dose of infected leukemic cells (vaccine). The reaction was not only directed against the infected leukemia cells, but against all of the leukemia cells in general. It was demonstrated that a single infusion was well tolerated and was not associated with any unacceptable side-effects. Also, the Phase I trial indicated therapeutic benefits, such as reduction in leukemia cell counts, lymph node size, and spleen size. We continue to follow the patients on this study; some have moved on to chemotherapy treatments, and others have received a second dose of the vaccine.

A Phase Ib extension trial was done for some of the patients who participated in the Phase I trial. This trial allowed for participating patients to receive re-treatment with repeated doses of the vaccine. This provided us with additional information, as we intend to give the vaccine as multiple-dose treatment. This also enabled us to have more information on the side effect profile and toxicities associated with repeated doses, and I am happy to report that the repeated doses were very well tolerated and also associated with a drop in leukemia counts and reduction in lymph node size.

A collaboration with Dr. Deepa Sampath at MD Anderson Cancer Center has also developed as a result of this clinical trial. The foundation for this collaboration is the observation that the leukemia cells become more sensitive to chemotherapy after patients received their modified leukemia cells. The basis for this sensitivity is being studied.

The Phase II clinical trial has been approved by the MD Anderson Cancer Center's Institutional Review Board. The Phase II trial will be 5 repeated doses of the patients' own leukemia cells that are modified to express ISF35. The focus of our work will be to study both the immune reaction that develops against the leukemia cells as a result of this treatment and at the sensitivity the leukemia cells develop to chemotherapy as a result of the treatment.