Vaccination with dendritic cell/tumor fusions following autologous stem cell transplant induces immunologic and clinical responses in multiple myeloma patients

Clin Cancer Res. 2013 Jul 1;19(13):3640-8. doi: 10.1158/1078-0432.CCR-13-0282. Epub 2013 May 17.

Abstract

Purpose: A multiple myeloma vaccine has been developed whereby patient-derived tumor cells are fused with autologous dendritic cells, creating a hybridoma that stimulates a broad antitumor response. We report on the results of a phase II trial in which patients underwent vaccination following autologous stem cell transplantation (ASCT) to target minimal residual disease.

Experimental design: Twenty-four patients received serial vaccinations with dendritic cell/myeloma fusion cells following posttransplant hematopoietic recovery. A second cohort of 12 patients received a pretransplant vaccine followed by posttransplant vaccinations. Dendritic cells generated from adherent mononuclear cells cultured with granulocyte macrophage colony-stimulating factor, interleukin-4, and TNF-α were fused with autologous bone marrow-derived myeloma fusion cells using polyethylene glycol. Fusion cells were quantified by determining the percentage of cells that coexpress dendritic cell and myeloma fusion antigens.

Results: The posttransplant period was associated with reduction in general measures of cellular immunity; however, an increase in CD4 and CD8(+) myeloma-specific T cells was observed after ASCT that was significantly expanded following posttransplant vaccination. Seventy-eight percent of patients achieved a best response of complete response (CR)+very good partial response (VGPR) and 47% achieved a CR/near CR (nCR). Remarkably, 24% of patients who achieved a partial response following transplant were converted to CR/nCR after vaccination and at more than 3 months posttransplant, consistent with a vaccine-mediated effect on residual disease.

Conclusions: The posttransplant period for patients with multiple myeloma provides a unique platform for cellular immunotherapy in which vaccination with dendritic cell/myeloma fusion fusions resulted in the marked expansion of myeloma-specific T cells and cytoreduction of minimal residual disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology*
  • Dendritic Cells / immunology*
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunity, Cellular
  • Immunotherapy
  • Male
  • Middle Aged
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / therapy*
  • Remission Induction
  • Transplantation, Autologous
  • Treatment Outcome
  • Vaccination

Substances

  • Cancer Vaccines