Vaccines in cancer: GVAX, a GM-CSF gene vaccine.
GVAX is a granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transfected tumor cell vaccine. Original work with GM-CSF as a recombinant DNA protein (Leukine) involved proliferative stimulation of macrophages and neutrophils for the purpose of reducing hematopoietic toxicity related to dose-intensive chemotherapy. Following US Food and Drug Administration approval of Leukine several years ago, extensive preclinical results have demonstrated an immunostimulatory effect related to GM-CSF gene when transfected into tumor cells and used as a vaccine (GVAX). Tumor regression and prolonged survival was demonstrated in animal models. Toxicology with GVAX indicated no adverse effects, which enabled further testing in cancer patients. A small number of responses were demonstrated in Phase I trials in immunosensitive cancer patients (renal cell carcinoma and melanoma). However, a series of dramatic complete and durable responses in advanced non-small cell lung cancer patients, demonstrated in recent clinical trials, have generated interest in further development of this vaccine in nontraditional cancer disease types. The rationale of GVAX development and a summary of clinical results are reviewed.
Nemunaitis
John
J
jnemunaitis@mcmrc.com
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans
D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor