通过树突状细胞疫苗接种使恶性胶质瘤对化疗敏感化。
Sensitization of malignant glioma to chemotherapy through dendritic cell vaccination.
作者信息
Liu Gentao, Black Keith L, Yu John S
机构信息
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, and Division of Hematology/Oncology, Cedars-Sinai Medical Center/David Geffen Schol of Medicine at UCLA, 8700 Beverly Blvd, Los Angeles, CA 90048, USA.
出版信息
Expert Rev Vaccines. 2006 Apr;5(2):233-47. doi: 10.1586/14760584.5.2.233.
Drug resistance represents a major cause of chemotherapy failure in patients with cancer. The characterization of the molecular pathways involved in drug resistance has provided new targets to circumvent or reverse chemotherapy resistance. Many of these target proteins are often overexpressed in human glioma and have been identified as tumor antigens, which implicate the development of immunotherapy as a therapeutic strategy. Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system and have been demonstrated to stimulate antibody and cell-mediated immune responses against tumor-associated antigens. Ex vivo-generated and tumor antigen-loaded DCs have been successfully introduced to clinical vaccination protocols, which have proven to be feasible and effective in some glioma patients. Most importantly, immunotherapy followed by chemotherapy could significantly increase 2-year survival in malignant glioma patients, which obviously demonstrates that DC vaccination could increase the sensitivity of tumor cells to chemotherapy. This review focuses on recent advances in the identification of tumor-associated antigen in glioma, as well as novel insights into their biological function related to drug resistance. These insights may provide the rationale for a novel strategy of a DC cancer vaccine that sensitizes tumor cells to chemotherapy. In addition, the current research status and the future direction of a DC-based vaccine to treat glioma in animal models and clinical trials will also be discussed.
耐药性是癌症患者化疗失败的主要原因。对耐药相关分子途径的表征提供了新的靶点,以规避或逆转化疗耐药性。这些靶点蛋白中的许多在人类胶质瘤中经常过度表达,并已被确定为肿瘤抗原,这意味着免疫疗法可作为一种治疗策略来发展。树突状细胞(DCs)是免疫系统中最强大的抗原呈递细胞,已被证明能刺激针对肿瘤相关抗原的抗体和细胞介导的免疫反应。体外生成并负载肿瘤抗原的DCs已成功应用于临床疫苗接种方案,在一些胶质瘤患者中已证明是可行和有效的。最重要的是,免疫疗法联合化疗可显著提高恶性胶质瘤患者的2年生存率,这明显表明DC疫苗接种可提高肿瘤细胞对化疗的敏感性。本综述重点关注胶质瘤中肿瘤相关抗原鉴定的最新进展,以及对其与耐药性相关生物学功能的新见解。这些见解可能为一种使肿瘤细胞对化疗敏感的DC癌症疫苗新策略提供理论依据。此外,还将讨论基于DC的疫苗在动物模型和临床试验中治疗胶质瘤的当前研究现状和未来方向。