title: TRICOM vector based cancer vaccines.
abstract: For the immune system to mount an effective antitumor T-cell response, an adequate number of T-cells specific for the antigens expressed by the malignancy must be activated [1]. Since most antigens expressed by tumors are "self"-antigens, tumor antigens often lack endogenous immunogenicity and thus do not sufficiently activate T-cells to levels that can mediate tumor eradication. In addition, virtually all solid tumor cells lack the costimulatory molecules necessary to activate tumor-specific T-cells. Approaches that stimulate immune responses to these tumor antigens have the potential to alter this poor responsiveness. This theory has promoted the use of active immunotherapy to generate immune responses against tumor-associated antigens (TAAs) for the treatment of cancer. As one such vaccine strategy, we have utilized poxviruses as delivery vehicles for TAAs in combination with T-cell costimulatory molecules. Initial studies have demonstrated that the insertion of costimulatory molecule trangenes into viral vectors, along with a TAA transgene, greatly enhances the immune response to the antigen. Using this approach, a TRIad of COstimulatory Molecules (TRICOM; B7-1, ICAM-1 and LFA-3) has been shown to enhance T-cell responses to TAAs to levels far greater than any one or two of the costimulatory molecules in combination. In this article, preclinical findings and recent clinical applications of TRICOM-based vaccines as a cancer immunotherapy are reviewed.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute/NIH, Bldg. 10, Rm. 8B09, 10 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Charlie T
authors.initials: CT
authors.lastname: Garnett
authors.forename: John W
authors.initials: JW
authors.lastname: Greiner
authors.forename: Kwong-Yok
authors.initials: KY
authors.lastname: Tsang
authors.forename: Chie
authors.initials: C
authors.lastname: Kudo-Saito
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Grosenbach
authors.forename: Mala
authors.initials: M
authors.lastname: Chakraborty
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: James W
authors.initials: JW
authors.lastname: Hodge
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000503:physiopathology / Q000517:prevention & control / Q000532:radiotherapy / Q000628:therapy*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000627:therapeutic use
chemical_list: D019496:Cancer Vaccines; D014614:Vaccines, Synthetic