Abstract | PURPOSE: 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.
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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)
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Copyright | ©2013 AACR. |
Chemical References |
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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
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