VACCINE THERAPY FOR MULTIPLE MYELOMA UTILIZING ALLOGENEIC DENDRITIC CELLS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypotheses: 1. Vaccination with allogeneic idiotype-pulsed dendritic cells following non-myeloablative allogeneic transplantation for multiple myeloma will be feasible and safe in treatment of this disease. 2. Vaccinated patients will mount a measurable idiotypic-specific immune response. Experimental Design: This Phase I/II study will evaluate primarily the feasibility and safety in thirty patients with multiple myeloma who will be vaccinated with allogeneic dendritic cell autologous Id-KLH vaccine. Patients with multiple myeloma with pre-transplant serum monoclonal para protein of the IgG isotype and who are eligible for transplantation are identified for vaccination. Prior to completing standard chemotherapy, peripheral blood is collected for vaccine development. Immunoglobulin will be isolated from patient serum by column chromatography, concentrated and the purified Id-protein will be sterile filtered prior to conjugation with KLH. The conjugation of the 60 mg purified Id-protein to KLH will be performed under aseptic conditions using glutaraldyde as the cross-linking agent prior to dendritic cell pulsing. Using recently developed methods for the isolation of human dendritic cells from peripheral blood, these cells will be taken from the non-myeloablative transplant donor. The allodonor will consent for apheresis specimen collection at the time that consent is obtained for transplant specimen collection. The apheresis product for dendritic cell preparation, however, will not be obtained until the recipient has successfully completed tandem transplant. An automated production process using the Aastrom Replicell System (ARS) device to grow dendritic cells will expand the patient's dendritic cell population. Primary incubation for 6 days is accomplished in the incubator at 37 0C with refrigerated medium supplemented by cytokines (GM-CSF at a concentration of 280 Units/mL and IL4 at 725 Units/mL). The Id-KLH protein (60 mg of Id conjugated to KLH at 1 mg/mL) will then be loaded into the ARS with aseptic technique. The secondary maturation incubation lasts for 48 hrs after which the cells are automatically harvested from the processor. After harvest, the cells will be washed to remove cytokines and other materials then cryopreserved in 20% DMSO and autologous plasma in single-use aliquots with 10 x 106 cells per vial. One single-use aliquot of cryopreserved cells selected at random will be tested for bacterial, fungal, and mycoplasma contamination along with endotoxin content. Dendritic cells pulsed with Id-KLH will be resuspended at a minimum concentration of 1 x106 viable cells in 1 mL of 0.9% saline and given by intradermal administration. Sites of administration will be systematically alternated with each vaccine. The first vaccination will occur between 9 and 18 months following allogeneic transplant and five subsequent vaccinations will be given on a once-monthly schedule.