Therapeutic effects of idiotype vaccination can be enhanced by the combination of granulocyte-macrophage colony-stimulating factor and interleukin 2 in a myeloma model

Br J Haematol. 2003 Jan;120(1):27-35. doi: 10.1046/j.1365-2141.2003.03930.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Antigens, Tumor-Associated, Carbohydrate / administration & dosage*
  • Cancer Vaccines / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Immunoglobulin Idiotypes / administration & dosage*
  • Interleukin-2 / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Multiple Myeloma / immunology
  • Multiple Myeloma / therapy*
  • Neoplasms, Experimental
  • Survival Rate
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured

Substances

  • Adjuvants, Immunologic
  • Antigens, Tumor-Associated, Carbohydrate
  • Cancer Vaccines
  • Immunoglobulin Idiotypes
  • Interleukin-2
  • Granulocyte-Macrophage Colony-Stimulating Factor