title: Vaccination with dendritic cell/tumor fusions following autologous stem cell transplant induces immunologic and clinical responses in multiple myeloma patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. jrosenb1@bidmc.harvard.edu
authors.forename: Jacalyn
authors.initials: J
authors.lastname: Rosenblatt
authors.forename: Irit
authors.initials: I
authors.lastname: Avivi
authors.forename: Baldev
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authors.lastname: Vasir
authors.forename: Lynne
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authors.lastname: Uhl
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.forename: Tami
authors.initials: T
authors.lastname: Katz
authors.forename: Bimalangshu R
authors.initials: BR
authors.lastname: Dey
authors.forename: Poorvi
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authors.lastname: Somaiya
authors.forename: Heidi
authors.initials: H
authors.lastname: Mills
authors.forename: Federico
authors.initials: F
authors.lastname: Campigotto
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.forename: Robin
authors.initials: R
authors.lastname: Joyce
authors.forename: James D
authors.initials: JD
authors.lastname: Levine
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tzachanis
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.forename: Jacob
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authors.lastname: Laubach
authors.forename: Noopur
authors.initials: N
authors.lastname: Raje
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Boussiotis
authors.forename: Yan Emily
authors.initials: YE
authors.lastname: Yuan
authors.forename: Lina
authors.initials: L
authors.lastname: Bisharat
authors.forename: Viki
authors.initials: V
authors.lastname: Held
authors.forename: Jacob
authors.initials: J
authors.lastname: Rowe
authors.forename: Kenneth
authors.initials: K
authors.lastname: Anderson
authors.forename: Donald
authors.initials: D
authors.lastname: Kufe
authors.forename: David
authors.initials: D
authors.lastname: Avigan
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy*; D012074:Remission Induction; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines