Morse M A
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Curr Opin Mol Ther. 2001 Aug;3(4):407-12.
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].
赛立昂生物公司、美国国立癌症研究所（NCI）和安万特巴斯德公司正在研究CEA-TRICOM，这是一种基于痘病毒的重组疫苗，它包含三剂共刺激分子以及癌胚抗原（CEA）肿瘤抗原，用于潜在治疗结直肠癌。CEA-TRICOM旨在刺激和增强人体免疫系统以杀死结直肠癌细胞。CEA-TRICOM采用一种启动和加强方案进行给药，使用两种独特的痘病毒载体，即rV-CEA-TRICOM（重组痘苗病毒载体）和rF-CEA-TRICOM（重组鸡痘病毒载体）。rV-CEA-TRICOM和rF-CEA-TRICOM的TRICOM成分均包含三个共刺激分子转基因（B7-1、ICAM-1和LFA-3）[414643]、[414645]，已知这些转基因能引发完全摧毁肿瘤所需的强烈细胞免疫反应。在美国国立癌症研究所和赛立昂生物公司进行的临床前研究中，研究人员已证明这三种共刺激分子的组合能显著增强免疫反应，从而在小鼠模型中根除癌症[399610]、[414631]。2001年2月，赛立昂生物公司和美国国立癌症研究所启动了CEA-TRICOM的I期试验[399610]。CEA-TRICOM的I期试验旨在证明将多种共刺激分子与肿瘤抗原联合使用以提高细胞免疫反应强度的原理。这是一项多阶段、剂量递增研究，将评估CEA-TRICOM在多达42名晚期转移性结直肠癌患者中的安全性和免疫效果。受试者将单独接受rF-CEA-TRICOM，或先接受rV-CEA-TRICOM，随后用rF-CEA-TRICOM进行加强接种，或先接受rV-CEA-TRICOM，随后接受rF-CEA-TRICOM和GM-CSF佐剂。免疫反应的主要衡量指标将是接种疫苗刺激产生的CEA特异性T细胞水平，血液中表达CEA的肿瘤细胞水平用作治疗效果的潜在次要衡量指标[399610]。
