Thomas J. Kipps M.D., Ph.D. University of California, San Diego Rebecca and John Moores Cancer Center

Gene and Vaccine Therapy

CLL Vaccines

Grant awarded in 2008

Abstract:

We discovered that the leukemia cells of all patients with CLL have a protein on their surface called ROR1. This protein is an enzyme that is normally present only on cells in fetal life and is not found on normal lymphcytes, including the lymphocytes from which the CLL cells are believed to have originated.

We made this discovery by examining the anti-leukemia antibodies made by patients who had received infusions of their own CLL cells, which were genetically engineered to make an immune stimulant (called CD154) in gene therapy studies conducted at UCSD. The anti-leukemia antibodies made by some of these patients reacted with leukemia cells, but not normal lymphocytes. Some of these antibodies reacted with ROR1 to shut off the capacity of this enzyme to promote leukemia-cell survival. As such, ROR1 represents a leukemia-specific antigen that can be targeted by the immune system to generate an anti-leukemia immune response in patients with CLL.

We are developing novel cancer vaccines that can induce specific immune responses against ROR1. These vaccines will be tested in the laboratory and in experimental animals to determine which of these vaccines is/are most effective in inducing an immune response against the leukemia cells of patients with CLL. The best candidate vaccine(s) will be made in sufficient quantities to perform preclinical studies that are required by the Federal Food and Drug Administration to allow for clinical studies in patients with CLL. It is projected that at the end of the two-year period of funding, we will have an optimized vaccine for clinical studies in patients with CLL.