B cell lymphomas display unique immunoglobulin receptors on their cell surface, and the idiotypic (Id) determinants of these proteins can be effectively targeted by the immune system. In prior animal studies and in human clinical trials, we have demonstrated that vaccination with Id determinants can induce both humoral and cellular immunity. This immunity can confer both protection against tumor challenge and can cause regression of pre-existing disease. Different methods of immunization can affect both the strength of a developing immune response as well as the balance of the resulting cellular and humoral components. This proposed project is part of our ongoing studies to investigate the use of a vaccination approach in the treatment of human B cell lymphoma. New techniques have been recently developed which have allowed the isolation and purification of human dendritic cells (DC) from peripheral blood. These cells are powerful antigen presenting cells, and when pulsed with antigen, they can be used to sensitize naive T cells, in vitro, leading to potent antigen specific immune responses. In animal studies, these cells have been shown to induce strong protective immune responses to tumor antigens. To study potential clinical applications we have initiated a pilot study investigating the use of Id pulsed DC as a vaccine in patients with B cell lymphoma. In our four evaluable patients, we have found that antigen pulsed DC are potent stimulators of Id specific cellular immune responses. Significantly, our first patient, who had measurable disease, subsequently underwent tumor regression after completing vaccine treatments and is in complete remission approximately two years later. A second patient had a partial tumor regression, and a third patient resolved all molecular evidence of disease. In this project, we propose to further investigate this approach in patients with B cell lymphoma. Participating patients will receive repeated infusions of autologous Id pulsed DC, and their cellular and humoral immune response to Id as well as changes in tumor burden will be monitored. The results of this study should not only determine whether antigen pulsed DC induce effective anti-tumor immunity but also whether the appearance and nature of Id specific immune responses correlate with tumor regression.
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