Craig Okada, MD

Tumor Antigen Receptor Vaccines for Active Immunotherapy of T Cell Malignancies

One of the most promising areas of cancer research is the use of immunotherapies-therapies that capitalize on the body’s own immune defenses. An important avenue of immunotherapy research is the use of vaccines to stimulate the immune system to mount its own attack against tumors. Dr. Okada has done preliminary research in the development of a vaccine for patients with T cell malignancies (malignancies that affect specialized immune cells known as T cells found in the blood and lymphoid tissues). T cell malignancies include some forms of leukemia and some non-Hodgkin’s lymphomas. Among lymphomas, peripheral and cutaneous T cell lymphoma are particularly deadly. Normal T cells have antigen receptors on their surface (called TCR, for T cell antigen receptor), which allow them to recognize and bind to antigens, thus triggering an immune response. These antigen receptors have determinants, called idiotypes, unique to the type of lymphocyte and the antigen. The unique configuration of the TCR means that the immune system can mount a specific attack against a particular antigen without harming other cells. Tumor cells also have antigen receptors on their surfaces. Because T cell lymphomas are clonal, the cells of the T cell lymphoma all contain the same unique antigen receptor, making it an ideal target for a vaccine. Thus, if an idiotype-specific TCR vaccine could be developed and injected, it should lead to a specific immune response directed at the tumor. Dr. Okada’s preliminary experiments with idiotype TCR vaccines in a mouse model have been promising. The chief obstacle is producing sufficient quantities of idiotype TCR vaccines and generating a more potent immune response. Dr. Okada is proposing further research to develop new idiotype TCR based vaccines and evaluate their efficacy in a mouse model. By examining and characterizing the specific immune response that is generated, he hopes to find ways to increase the ability of these vaccines to generate a potent and specific immune response against T cell lymphomas. Ultimately, this work may lead to effective TCR vaccines for human T cell lymphomas.