Therapeutic effects of idiotype vaccination can be enhanced by the combination of granulocyte-macrophage colony-stimulating factor and interleukin 2 in a myeloma model.
Idiotype (Id) vaccination provides an interesting immunotherapeutic strategy against B-cell lymphomas. In multiple myeloma (MM), however, the therapeutic efficacy of Id vaccination has been disappointing. In an attempt to improve the antitumoral potential, we added granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 2 (IL-2) to the protocol. Balb/c mice were inoculated i.p. (d 2) with different doses (1-5 x 10(5)) of HOPC myeloma cells secreting the Ig(HOPC) Id protein. Two days later, animals were injected with 10,000 U GM-CSF i.p. for 6 d consecutively (d 0-5). On d 5 and 11, myeloma-specific immunoglobulin (Ig(HOPC)) was administered i.p. together with incomplete Freund adjuvans followed by IL-2 (2 x 10,000 U/d; i.p) for 10 d (d 5-14). In animals inoculated with 10(5) myeloma cells, treatment with IL-2 given as a single agent prolonged the median survival time (MST, 67 d) when compared with the tumour control group (MST 48 d), whereas GM-CSF did not elicit any survival benefit (MST 49 d). Complete tumour rejection could be achieved in 27% (4/15) by the combination of Id vaccination and GM-CSF. Additional treatment with IL-2 further increased antimyeloma activity. In this case, 59% of the animals showed no signs of tumour recurrence. In mice with high tumour burden (5 x 10(5)), no treatment modality achieved long-term survivors. Both natural killer (NK) cells and CD8+ T cells may be involved in the anti-tumoural immune response. These data provide evidence for the combined use of GM-CSF and IL-2 to enhance the therapeutic effectiveness of clinical cancer vaccination protocols.
Stritzke
Jan
J
Institute of Immunology, University of Kiel, Germany.
Zunkel
Tim
T
Steinmann
Jörg
J
Schmitz
Norbert
N
Uharek
Lutz
L
Zeis
Matthias
M
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000008:administration & dosage*; D019496:Cancer Vaccines / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D007130:Immunoglobulin Idiotypes / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*; D009374:Neoplasms, Experimental; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D015295:Antigens, Tumor-Associated, Carbohydrate; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor