Idiotype protein-pulsed dendritic cells produce strong anti-myeloma effects after syngeneic stem cell transplantation in mice.
Dendritic cell (DC) vaccination represents an interesting immunotherapeutic option in the treatment of several malignancies. In multiple myeloma (MM) patients, vaccination with autologous idiotype (Id) protein-pulsed DC is feasible, but their antitumoral effectiveness was rather limited. To improve the therapeutic potential of DC therapy, we studied the immunological effects of syngeneic peripheral blood stem cell transplantation (PBSCT) given in conjunction with Id-loaded DC. Balb/c mice were inoculated i.p. with 5 x 10(5) of HOPC myeloma cells (Balb/c origin). Animals were immunized with three injections of 5 x 10(5) DC pulsed with the IgG2a(HOPC) or with a control immunoglobulin (Ig(control)). Some experimental groups of myeloma-bearing animals received total body irradiation (7.5 Gy) and a subsequent transplant of 2 x 10(7)syngeneic peripheral blood progenitor cells (PBPC) followed by DC therapy beginning at day 10 post transplant. Animals receiving DC therapy or syngeneic PBPCT alone neither induce long-term survival nor tumor-specific CTL reactivity in vitro. In marked contrast, combination of syngeneic PBPC transplantation and subsequent DC therapy resulted in 78% survival after a follow-up of 180 days. In addition, this treatment modality conferred a generation of Id peptide-specific CD8-mediated T cell reactivity. These data provide a rationale for DC-based vaccination in multiple myeloma patients administered post syngeneic transplantation.
Zeis
M
M
Department of Internal Medicine II, University of Kiel, Germany.
Frenzke
H
H
Schmitz
N
N
Uharek
L
L
Steinmann
J
J
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D018929:Cell Culture Techniques / Q000379:methods; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D007130:Immunoglobulin Idiotypes / Q000276:immunology* / Q000627:therapeutic use; D016219:Immunotherapy, Adoptive / Q000379:methods* / Q000401:mortality; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic; D014185:Transplantation, Isogeneic / Q000379:methods / Q000401:mortality; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000951:Antigens, Neoplasm; D007130:Immunoglobulin Idiotypes