Immunotherapy of cancer.
The goal of cancer treatment is to develop modalities that specifically target tumor cells, thereby avoiding unnecessary side effects to normal tissue. Vaccine strategies that result in the activation of the immune system specifically against proteins expressed by a cancer have the potential to be effective treatment for this purpose. An early vaccine approach that was developed by our group involves the insertion of the granulocyte-macrophage colony stimulating factor (GM-CSF) gene into cancer cells that are then used to immunize patients. These genetically modified tumor cells produce the immune activating protein GM-CSF in the local environment of the tumor cells, specifically activating the patient's T cells to eradicate cancer at metastatic sites. We have performed many studies that demonstrate that this vaccine can cure mice of cancer. We recently demonstrated that this approach can activate an immune response in patients with renal cell carcinoma. We are currently testing a similar approach in patients with pancreatic cancer. Until recently, whole tumor cells were used to produce the vaccine because the proteins expressed by the tumor cells that can be recognized by the immune system were unknown. However, recent advances have allowed the identification of many of the proteins expressed by some cancers. In addition, significant attention has been focused on the mechanisms by which antitumor immunity can be modulated. These active areas of research will undoubtably lead to the development of more specific and more potent vaccine strategies in the near future. The first part of this paper focuses on data from two recent clinical trials that evaluated the whole tumor cell approach. The second part of this paper discusses some of the more exciting antigen-specific vaccine approaches that are under development for the treatment of cancer.
Jaffee
E M
EM
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor