B-cell lymphoma and myeloma protection induced by idiotype vaccination with dendritic cells is mediated entirely by T cells in mice.
Immunoglobulin idiotypes (Id) of malignant B cells are tumor-specific antigens that may be targeted for immunotherapy. Id-directed immunotherapy by immunization with autologous Id has been initiated in clinical trials to control residual disease in B-cell lymphoma and multiple myeloma. The effector mechanisms responsible for destruction of B-cell tumors are a controversial issue. The authors show that vaccination with Id-pulsed dendritic cells (DCs) or with soluble Id-KLH in adjuvant induced immune responses that eliminated both B-cell lymphoma and myeloma in tumor-bearing mice; however, the two vaccination regimens resulted in distinct immune responses. Whereas soluble Id plus adjuvant induced high levels of anti-Id antibodies, the Id-pulsed DCs did not induce anti-Id or any antitumor antibodies. Immunization with Id-pulsed DCs induced a significant increase in the frequency of Id-reactive T cells. Depletion studies in DC-vaccinated mice showed that the predominant effector cells responsible for tumor rejection were of the CD8 subset. The finding that DC-based Id vaccines elicit tumor protection, which is entirely based on cell-mediated effector mechanisms, is of particular importance for plasma cell tumors because these tumors do not express Id on the surface and hence do not bind anti-Id antibodies.
Cohen
Sharon
S
Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Haimovich
Joseph
J
Hollander
Nurit
N
D000818:Animals; D000912:Antibodies, Neoplasm / Q000737:chemistry; D000951:Antigens, Neoplasm / Q000737:chemistry; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007130:Immunoglobulin Idiotypes; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008856:Microscopy, Fluorescence; D009101:Multiple Myeloma / Q000628:therapy*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013997:Time Factors; D014162:Transfection
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D007371:Interferon-gamma