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

Gene and Vaccine Therapy

Gene Therapy with ISF-35 Transduced Autologous CLL Cell Vaccine

Grant Awarded in 2008

Abstract:

CLL is currently considered incurable with standard treatments. Complete remission can be achieved in the majority of previously untreated patients with the first treatment; however, their disease will eventually return. To make further progress in treatment of patients with CLL, new treatments with novel and complementary mechanisms of action to chemotherapy are needed.

Immune-based therapy holds great potential as a new treatment and is the premise of this project. In this immune-based therapy, leukemia cells from patients with CLL are taken and exposed in the laboratory to a genetically altered virus that carries a gene for a protein (ISF35) that can function as an immune-stimulating protein.

Upon infection with this virus, the CLL cells express the ISF35 on their surface and in doing so, acquire the ability to stimulate the immune system to react against the leukemia cells. These cells are given back to the patient as a vaccine to stimulate the patients' own immune system to react against and eliminate the leukemia. We have done a clinical trial with a single dose of modified cells and showed that this is a safe and active strategy for treatment.

We have planned a clinical trial with repeated infusions of the modified cells to evaluate the effectiveness of this treatment strategy in treating patients with CLL. In this trial, 20 patients will receive a total of 5 infusions of modified cells. The working hypothesis is that clinically significant, sustained remissions will be observed in patients treated with repeated doses of ISF35-modified leukemia cells that result from immune-mediated responses against the leukemia cells.