Department of Microbiology and Immunology, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul, Korea.
Cancer Immunol Immunother. 2010 May;59(5):747-57. doi: 10.1007/s00262-009-0795-3.
Topoisomerase II alpha (Top2alpha) is an attractive candidate to be used as a tumor antigen for cancer immunotherapy, because it is abundantly expressed in various tumors and serves as a target for a number of chemotherapeutic agents. In this study, we demonstrated the immunogenicity of Top2alpha, using dendritic cells (DC) electroporated with RNA encoding the Top2alpha C-terminus (Top2alphaCRNA/DC). Top2alphaCRNA/DC were able to demonstrate in vitro stimulation of T cells from mice that were previously vaccinated with Top2alpha-expressing tumor lysate-pulsed DC. Vaccination with Top2alphaCRNA/DC induced Top2alpha-specific T cell responses in vivo as well as antitumor effects in various murine tumor models including MC-38, B16F10, and GL26. DC pulsed with p1327 (DSDEDFSGL), defined as an epitope presented by H-2K(b), also induced Top2alpha-specific immune responses and antitumor effects. Based on these data, Top2alpha is suggested to be a universal target for cancer immunotherapy.
拓扑异构酶 IIα(Top2α)是一种有吸引力的肿瘤抗原候选物,可用于癌症免疫治疗,因为它在各种肿瘤中大量表达,并成为许多化疗药物的靶标。在这项研究中,我们使用编码 Top2α C 末端的 RNA 转染的树突状细胞(DC)(Top2αCRNA/DC)证明了 Top2α 的免疫原性。Top2αCRNA/DC 能够体外刺激先前用表达 Top2α 的肿瘤裂解物脉冲的 DC 接种的小鼠的 T 细胞。用 Top2αCRNA/DC 接种可在体内诱导 Top2α 特异性 T 细胞反应,并在包括 MC-38、B16F10 和 GL26 在内的各种小鼠肿瘤模型中产生抗肿瘤作用。用 p1327(DSDEDFSGL)脉冲的 DC 也可诱导 Top2α 特异性免疫反应和抗肿瘤作用,p1327 定义为由 H-2K(b)呈递的表位。基于这些数据,Top2α 被认为是癌症免疫治疗的通用靶标。