Department of Oncology, Shanghai Pudong New Area Gongli Hospital, Shanghai 200127, China.
Shanghai Sunstem Biotechnology Co., Ltd., Pudong, Shanghai 200127, China.
J Healthc Eng. 2022 Apr 18;2022:1964081. doi: 10.1155/2022/1964081. eCollection 2022.
Dendritic cells (DCs) are antigen-presenting cells that can activate T cells and initiate a primary immune response. Personalized DC vaccines have demonstrated a modest antitumor potential in some clinical pilot studies. However, those vaccines are difficult to manufacture and have a limited antitumor response. In this study, a lentiviral vector-programmed DC vaccine with high antitumor responses is developed. By transfecting with a lentiviral vector, the DC vaccine is loaded with MG-7 antigen (MG-7Ag). Three representative gastric cancer cell lines, such as KATO-3, MKN45, and SNU16, are used to estimate the in vitro cytotoxic effect of the MG-7Ag DC vaccine. Furthermore, we examine the in vivo antitumor efficacy of specific cytotoxic T lymphocytes (CTLs) induced by the MG-7Ag DC vaccine in patient-derived xenograft (PDX) mice models. The current data demonstrate that the MG-7Ag DC vaccine induced a potent CTL activity. Those CTLs have a significant cytotoxic effect on both KATO-3 and MKN45 with high level of MG-7 expression. In addition, MG-7Ag DC vaccine-mediated CTLs significantly inhibit the growth of tumor xenografts in nude mice. The MG-7Ag DC vaccine activate the cytotoxic effect of lymphocytes and can be employed as a vaccine in gastric cancer immunotherapy.
树突状细胞（DCs）是一种能够激活 T 细胞并引发初始免疫应答的抗原呈递细胞。个性化的 DC 疫苗在一些临床初步研究中显示出了一定的抗肿瘤潜力。然而，这些疫苗的制造难度较大，且抗肿瘤反应有限。在本研究中，开发了一种具有高抗肿瘤反应的基于慢病毒载体的 DC 疫苗。通过慢病毒载体转染，将 DC 疫苗负载 MG-7 抗原（MG-7Ag）。使用三种代表性的胃癌细胞系，如 KATO-3、MKN45 和 SNU16，评估 MG-7Ag DC 疫苗的体外细胞毒性效应。此外，我们在患者来源的异种移植（PDX）小鼠模型中研究了 MG-7Ag DC 疫苗诱导的特异性细胞毒性 T 淋巴细胞（CTLs）的体内抗肿瘤疗效。目前的数据表明，MG-7Ag DC 疫苗诱导了强烈的 CTL 活性。这些 CTLs 对高表达 MG-7 的 KATO-3 和 MKN45 具有显著的细胞毒性作用。此外，MG-7Ag DC 疫苗介导的 CTLs 显著抑制了裸鼠肿瘤异种移植的生长。MG-7Ag DC 疫苗激活了淋巴细胞的细胞毒性作用，可作为胃癌免疫治疗的疫苗。
