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Technology evaluation: CEA-TRICOM, Therion Biologics Corp
1Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. morse004@mc.duke.edu
Abstract:
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].
Insights
This study investigates CEA-TRICOM, a novel vaccine for colorectal cancer, using pox virus vectors to stimulate the immune system against tumor cells. Early trials assess safety and immune response in patients with advanced metastatic colorectal cancer.
Area of Science:
- Oncology
- Immunology
- Vaccine Development
Background:
- Colorectal cancer remains a significant health challenge, necessitating novel therapeutic strategies.
- Current treatments for advanced metastatic colorectal cancer have limitations.
- CARCINOEMBRYONIC ANTIGEN (CEA) is a tumor antigen expressed in colorectal cancer, making it a target for immunotherapy.
Purpose of the Study:
- To evaluate the safety and immunologic effects of CEA-TRICOM, a novel pox virus-based vaccine, in patients with advanced metastatic colorectal cancer.
- To demonstrate the proof-of-principle for using multiple costimulatory molecules with a tumor antigen to enhance cellular immune responses.
- To assess the efficacy of different vaccination protocols involving recombinant vaccinia and fowlpox vectors.
Main Methods:
- A Phase I, multistage, dose-escalation trial involving up to 42 patients with advanced metastatic colorectal cancer.
- Administration of CEA-TRICOM using a priming and boosting protocol with recombinant vaccinia (rV-CEA-TRICOM) and recombinant fowlpox (rF-CEA-TRICOM) vectors.
- Evaluation of different regimens including rF-CEA-TRICOM alone, rV-CEA-TRICOM followed by rF-CEA-TRICOM, and rV-CEA-TRICOM followed by rF-CEA-TRICOM with GM-CSF adjuvant.
Main Results:
- Preclinical studies in murine models demonstrated that the combination of three costimulatory molecules (B7-1, ICAM-1, LFA-3) significantly boosted immune response against cancer.
- The Phase I trial is designed to measure the level of CEA-specific T-cells stimulated by vaccination as the primary immune response measure.
- CEA-expressing tumor cells in the blood will be used as a secondary measure of treatment effect.
Conclusions:
- CEA-TRICOM represents a promising immunotherapy approach for colorectal cancer by leveraging the immune system to target tumor cells.
- The combination of tumor antigen and costimulatory molecules has the potential to elicit potent anti-tumor immune responses.
- Further clinical trials are warranted to establish the efficacy and optimal use of CEA-TRICOM in colorectal cancer treatment.