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1.
Br J Haematol ; 120(1): 27-35, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12492573

ABSTRACT

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.


Subject(s)
Antigens, Tumor-Associated, Carbohydrate/administration & dosage , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Immunoglobulin Idiotypes/administration & dosage , Interleukin-2/therapeutic use , Multiple Myeloma/therapy , Adjuvants, Immunologic/therapeutic use , Animals , Cancer Vaccines/administration & dosage , Mice , Mice, Inbred BALB C , Multiple Myeloma/immunology , Neoplasms, Experimental , Survival Rate , T-Lymphocytes, Cytotoxic/immunology , Tumor Cells, Cultured
2.
Br J Haematol ; 117(1): 93-102, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11918538

ABSTRACT

Idiotype (Id) vaccination provides an innovative treatment modality against B-cell malignancies. In multiple myeloma patients, however, the antitumoral potential of this immunotherapeutic concept is limited. In an attempt to improve the therapeutic effectiveness of Id vaccination, we added Flt3 ligand (Flt3-L) 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 IgHOPC Id-protein. Two days later, animals were treated with Flt3-L (10 microg per mouse/d, given i.p) for 10 consecutive days (d 0-9). On d 5 and d 11, myeloma-specific immunoglobulin (Ig(HOPC)) was administered s.c., together with incomplete Freund adjuvans (IFA) followed by the administration of IL-2 (2 x 10.000/d given i.p) for 10 d (d 5-14). Whereas Ig(HOPC), Flt3-L or IL-2, given alone, did not elicit long-term survival, the combination of IL-2 or Flt3-L with Id vaccination achieved a complete tumour rejection in 27% and 41% of mice respectively. However, the most powerful antimyeloma effects were induced by Flt3-L + Id vaccination + IL-2: 81% of the treated animals experienced long-term survival (> 180 d). Both natural killer (NK) cells and CD8+ T cells may be involved in the antitumoral immune response. These data suggest that the combination of Flt3-L and IL-2 can be used to enhance the therapeutic effectiveness of clinical cancer vaccination protocols.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Immunoglobulin Idiotypes/administration & dosage , Immunotherapy/methods , Interleukin-2/administration & dosage , Membrane Proteins/administration & dosage , Multiple Myeloma/therapy , Animals , Cytotoxicity Tests, Immunologic , Dendritic Cells/immunology , Injections, Intraperitoneal , Killer Cells, Natural/immunology , Mice , Mice, Inbred BALB C , Models, Animal , Multiple Myeloma/immunology , Spleen/immunology
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