IDIOTYPE VACCINATION AFTER BONE MARROW TRANSPLANTATION FOR B CELL MALIGNANCIES

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In this project we propose to treat patients with B cell malignancies (multiple myeloma or low grade lymphoma) with bone marrow transplantation followed by an attempt to induce an immune response against the tumor. Based on our prior work we will be using the immunoglobulin idiotype produced by each patient's tumor as the specific antigen. We will be taking advantage of a new method of immunization that we have developed using dendritic cells isolated from the blood as antigen presenting cells. Each patient will have the immunoglobulin produced by his/her tumor isolated and purified for use as a vaccine. High dose radio/chemotherapy will be administered and the patients will receive bone marrow or peripheral blood progenitor cell transplants. If a suitable matched sibling donor is available, allogeneic transplantation will be preferred. After recovery from the transplant procedure dendritic cells will be obtained by leukopheresis either from the donor, if one exists, or from the patient. These cells will be pulsed with the idiotype protein and then infused into the patient on two occasions, followed by a series of monthly injections of idiotype protein coupled to a carrier protein and mixed with an adjuvant. The patients will be evaluated for their immune response against the tumor and we will compare the patients receiving allogeneic dendritic cells to those receiving autologous dendritic cells. Special assays will be designed for the detection of cytotoxic T-cells directed against the tumor idiotype. The basic question posed in this project is whether an effective anti- tumor immune response can be induced in patients with B cell malignancies which can augment the therapeutic effect of high dose radio/chemotherapy followed by allogeneic or autologous hematopoietic precursor cell transplantation. Although we will be observing the clinical outcome of the transplant maneuver, the proposed studies are not designed to prove clinical efficacy. The primary endpoints will be the documentation of immune responses which we hope will be enhanced by allogeneic or autologous dendritic cells. If the initial pilot trials show promising results, appropriate prospective studies will be designed to demonstrate the efficacy of this novel approach.