Pervin S, Chakraborty M, Bhattacharya-Chatterjee M, Zeytin H, Foon K A, Chatterjee S K
Department of Obstetrics and Gynecology, University of Kentucky Medical Center, Lexington 40536-0096, USA.
Cancer Res. 1997 Feb 15;57(4):728-34.
Carcinoembryonic antigen (CEA) is a tumor-associated antigen expressed on most gastrointestinal adenocarcinomas and is a putative target for cancer immunotherapy. We developed a murine monoclonal anti-idiotype (anti-Id) antibody, 3H1, which mimics a specific epitope of CEA, for cancer immunotherapy. In this study, the efficacy of 3H1 as a tumor vaccine was evaluated in a murine tumor model. In this model, the murine colorectal cancer cell line MC-38 was transduced with the human CEA gene and injected into syngeneic C57BL/6 (H-2b) mice. Immunization of naive mice with 3H1 conjugated with keyhole limpet hemocyanin Freund's adjuvant induced humoral and cellular anti-3H1 as well as anti-CEA immunity. Mice immunized with 3H1 were protected against a challenge with lethal doses of MC-38-cea, whereas no protection was observed when 3H1 vaccinated mice were challenged with CEA negative MC-38 cells or when mice were vaccinated with an unrelated anti-Id antibody and challenged with MC-38-cea cells (P < 0.003). These data demonstrate that the 3H1 vaccine can induce protective CEA-specific antitumor immunity.
癌胚抗原（CEA）是一种在大多数胃肠道腺癌上表达的肿瘤相关抗原，是癌症免疫治疗的一个假定靶点。我们开发了一种模拟CEA特定表位的鼠源单克隆抗独特型（抗Id）抗体3H1，用于癌症免疫治疗。在本研究中，在鼠肿瘤模型中评估了3H1作为肿瘤疫苗的疗效。在该模型中，用人CEA基因转导鼠结肠癌细胞系MC-38，并将其注射到同基因C57BL/6（H-2b）小鼠体内。用与钥孔戚血蓝蛋白弗氏佐剂偶联的3H1免疫未免疫小鼠，可诱导体液和细胞抗3H1以及抗CEA免疫。用3H1免疫的小鼠可免受致死剂量的MC-38-cea攻击，而当用3H1疫苗接种的小鼠用CEA阴性的MC-38细胞攻击时，或当小鼠用无关抗Id抗体接种并被MC-38-cea细胞攻击时，未观察到保护作用（P<0.003）。这些数据表明，3H1疫苗可诱导具有保护作用的CEA特异性抗肿瘤免疫。
