Work

63: Vaccination with dendritic cell myeloma fusions alone or in conjunction with stem cell transplantation for patients with multiple myeloma

Year: 2007

Type: article

Abstract: We have demonstrated that patient derived myeloma cells fused with autologous dendritic cells (DCs) potently stimulate anti-tumor immunity in vitro. We are conducting phase I clinical trials in which patients with myeloma undergo serial vaccination with DC/myeloma fusions alone or in conjunction with stem cell transplantation. To date, 18 patients have been enrolled (11- vaccine alone, 7 vaccine following autologous stem cell transplant). To generate mature DCs, adherent mononuclear cells were isolated from a leukapharesis collection and cultured with GM-CSF, IL-4, and TNFα . The mean yield and viability of the DC preparations was 1.5 × 108 cells and 88%, respectively. Patient derived myeloma cells were isolated from bone marrow aspirates and were quantified by the expression of CD38 and/or CD138. The mean yield and viability of the myeloma cell collections was 7.3 × 107 cells and 89%, respectively. Fusion cells were generated by coculture of DCs with myeloma cells in the presence of 50% polyethylene glycol. The mean fusion efficiency was 40% as determined by the percentage of cells that co-expressed unique DC and myeloma antigens. In contrast to myeloma cells, the DC and fusion cell preparations prominently stimulated allogeneic T cell proliferation in vitro. To date, 13 patients have completed vaccination at a dose of 1-5 × 106 fusion cells. GM-CSF (100 μg) was administered subcutaneously on the day of vaccination and for 3 days thereafter. Adverse events judged to be potentially vaccine related have included vaccine injection site reactions, edema, rash, fever, chills, fatigue, muscle aches, pruritis, and diarrhea. One patient with a history of prior deep venous thrombosis (DVT) developed a DVT and pulmonary embolus of uncertain relation to the vaccine. To date, a majority of evaluable patients demonstrated evidence of vaccine induced anti-myeloma immunity as demonstrated by at least 2 fold increase in IFNγ expression by CD4 and/or CD8 T cells in response to ex vivo exposure to autologous tumor lysate. Of patients undergoing vaccine therapy alone, 5 patients demonstrated stabilization of the myeloma paraprotein for 2-6 months following initiation of vaccination. Of 3 patients completing post-transplant vaccination, 2 patients demonstrated resolution of the persisting myeloma protein post-transplant and 1 patient demonstrated a transient increase followed by a decline in paraprotein levels post-transplant.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2006.12.066