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

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.

• Authors: Jacalyn Rosenblatt, Irit Avivi, Baldev Vasir, Lynne Uhl, Nikhil C Munshi, Tami Katz, Bimalangshu R Dey, Poorvi Somaiya, Heidi Mills, Federico Campigotto, Edie Weller, Robin Joyce, James D Levine, Dimitrios Tzachanis, Paul Richardson, Jacob Laubach, Noopur Raje, Vassiliki Boussiotis, Yan Emily Yuan, Lina Bisharat, Viki Held, Jacob Rowe, Kenneth Anderson, Donald Kufe, David Avigan
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 19 Issue 13 Pg. 3640-8 (Jul 01 2013) ISSN: 1557-3265 [Electronic] United States
• PMID: 23685836 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2013 AACR.

Chemical References

• Cancer Vaccines

Topics

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