John M. Timmerman, MD

Anti-CTLA Monoclonal Antibody Therapy for B Cell Lymphoma

Most non-Hodgkin’s B cell lymphomas are resistant to cure with conventional chemotherapy. Paradoxically however, lymphomas are among the most susceptible of human cancers to destruction by immunologic mechanisms (T cells and antibodies). We are seeking to develop new ways to “jump start” the immune system of lymphoma patients to recognize and destroy their tumors. Lymphoma cells tend to shut down the immune system’s natural defenses against the tumor, and reversal of this process might thereby lead to inhibition of tumor growth. A molecule called CTLA-4 acts as the “brakes” on T cell activation, and blocking this molecule can result in heightened activation of immune responses. Administration of monoclonal antibodies that block CTLA-4 has been found to promote potent anti-tumor effects in animals with many types of cancers. In humans, a new monoclonal antibody which blocks CTLA-4 has been found to exhibit anti-tumor effects in melanoma and prostate cancer. Dr. Timmerman’s team is initiating the first clinical study of anti-CTLA-4 monoclonal antibody therapy for B cell lymphoma. In the laboratory, they will study how anti-CTLA-4 treatment activates patient’s T cells and antibodies to attack and destroy their tumor cells. It is hoped that anti-CTLA-4 therapy may then be combined with other immunotherapies including tumor vaccines and anti-tumor (i.e., anti-CD20) monoclonal antibodies to enhance their effectiveness. Such interventions could offer highly tumor-selective approaches to lymphoma treatment without the toxicities associated with conventional chemotherapeutic agents.