Department of Clinical Sciences and Translational Medicine Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Recent Pat Anticancer Drug Discov. 2012 Sep;7(3):265-96. doi: 10.2174/157489212801820020.
Carcinoembryonic antigen (CEA), a glycosylated protein of MW 180 kDa, is overexpressed in a wide range of human carcinomas, including colorectal, gastric, pancreatic, non-small cell lung and breast carcinomas. Accordingly, CEA is one of several oncofetal antigens that may serve as a target for active anti-cancer specific immunotherapy. Experimental results obtained by employing animal models have supported the design of clinical trials using a CEA-based vaccine for the treatment of different types of human cancers. This review reports findings from experimental models and clinical evidence on the use of a CEA-based vaccine for the treatment of cancer patients. Among the diverse CEA-based cancer vaccines, DCs- and recombinant viruses-based vaccines seem the most valid. However, although vaccination was shown to induce a strong immune response to CEA, resulting in a delay in tumor progression and prolonged survival in some cancer patients, it failed to eradicate the tumor in most cases, owing partly to the negative effect exerted by the tumor microenvironment on immune response. Thus, in order to develop more efficient and effective cancer vaccines, it is necessary to design new clinical trials combining cancer vaccines with chemotherapy, radiotherapy and drugs which target those factors responsible for immunosuppression of immune cells. This review also discusses relevant patents relating to the use of CEA as a cancer vaccine.
癌胚抗原(CEA)是一种糖蛋白,MW 为 180 kDa,在广泛的人类癌中过度表达,包括结直肠癌、胃癌、胰腺癌、非小细胞肺癌和乳腺癌。因此,CEA 是几种癌胚抗原之一,可能作为主动抗癌特异性免疫治疗的靶点。通过动物模型获得的实验结果支持了使用基于 CEA 的疫苗治疗不同类型人类癌症的临床试验的设计。本综述报告了基于 CEA 的疫苗用于治疗癌症患者的实验模型和临床证据的结果。在各种基于 CEA 的癌症疫苗中,基于树突状细胞和重组病毒的疫苗似乎最有效。然而,尽管疫苗接种显示可诱导针对 CEA 的强烈免疫应答,从而导致一些癌症患者的肿瘤进展延迟和生存时间延长,但在大多数情况下未能消除肿瘤,部分原因是肿瘤微环境对免疫应答的负面影响。因此,为了开发更有效和有效的癌症疫苗,有必要设计新的临床试验,将癌症疫苗与化疗、放疗和靶向那些导致免疫细胞免疫抑制的因素的药物相结合。本综述还讨论了与使用 CEA 作为癌症疫苗相关的相关专利。