Technology evaluation: CEA-TRICOM, Therion Biologics Corp

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.