Technology evaluation: CEA-TRICOM, Therion Biologics Corp.
Therion Biologics, the NCI and Aventis Pasteur are investigating CEA-TRICOM, a recombinant, pox virus-based vaccine that incorporates a triple dose of costimulatory molecules as well as the carcinoembryonic antigen (CEA) tumor antigen, for the potential treatment of colorectal cancer. CEA-TRICOM is designed to stimulate and strengthen the body's immune system to kill colorectal cancer cells. CEA-TRICOM is administered in a priming and boosting protocol using two unique pox virus vectors, rV-CEA-TRICOM (recombinant vaccinia vector) and rF-CEA-TRICOM (recombinant fowlpox vector). The TRICOM component of both rV-CEA-TRICOM and rF-CEA-TRICOM comprises three costimulatory molecule transgenes (B7-1, ICAM-1 and LFA-3) [414643], [414645], known to elicit strong cellular immune responses necessary for complete tumor destruction. In preclinical studies conducted by the NCI and Therion, researchers have demonstrated that this combination of three costimulatory molecules dramatically boosts the immune response to eradicate cancer in murine models [399610], [414631]. In February 2001, Therion Biologics and the NCI initiated a phase I trial of CEA-TRICOM [399610]. The phase I trial of CEA-TRICOM is designed to demonstrate proof-of-principle for using multiple costimulatory molecules in conjunction with a tumor antigen to improve the strength of cellular immune responses. It is a multistage, dose-escalation study that will assess the safety and immunologic effects of CEA-TRICOM in up to 42 patients who have advanced metastatic colorectal cancer. Subjects will receive rF-CEA-TRICOM alone, rV-CEA-TRICOM followed by booster vaccinations with rF-CEA-TRICOM or rV-CEA-TRICOM followed by rF-CEA-TRICOM and GM-CSF adjuvant. The primary measure of immune response will be the level of CEA-specific T-cells stimulated by vaccination, with levels of CEA-expressing tumor cells in the blood used as a potential secondary measure of treatment effect [399610].
Morse
M A
MA
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. morse004@mc.duke.edu
D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D002272:Carcinoembryonic Antigen; D019444:Vaccines, DNA; D014765:Viral Vaccines