Idiotype/granulocyte-macrophage colony-stimulating factor fusion protein as a vaccine for B-cell lymphoma.
To produce a vaccine against cancer, antigens must be found that are preferentially expressed by tumour cells and can induce an immune response against the tumour. The variable regions of the immunoglobulin molecules expressed on malignant B cells (idiotypes) are tumour-specific, but are weak immunogens. To induce an immune response in animals or humans, the idiotypic protein has therefore to be chemically coupled to a strongly immunogenic protein and mixed with an adjuvant. The resulting response can protect animals from subsequent tumour challenge, and cure animals with established tumours in combination with chemotherapy. Granulocyte-macrophage colony-stimulating factor (GM-CSF) augments antigen presentation in a variety of cells. Here we show that by fusing a tumour-derived idiotype to GM-CSF, it can be converted into a strong immunogen capable of inducing idiotype-specific antibodies without other carrier proteins or adjuvants and of protecting recipient animals from challenge with an otherwise lethal dose of tumour cells. This approach may be applicable to the design of vaccines for a variety of other diseases.
Tao
M H
MH
Department of Medicine, School of Medicine, Stanford University, California 94305.
Levy
R
R
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007167:Immunotherapy; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology; D009368:Neoplasm Transplantation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D014162:Transfection; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
D000888:Antibodies, Anti-Idiotypic; D000912:Antibodies, Neoplasm; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor