Song W, Tong Y, Carpenter H, Kong H L, Crystal R G
Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY, USA.
Gene Ther. 2000 Dec;7(24):2080-6. doi: 10.1038/sj.gt.3301336.
Dendritic cells (DC) are potent antigen-presenting cells that play a critical role in the initiation of cellular immune responses. Using a BALB/c syngeneic colon carcinoma cell line expressing a model tumor antigen beta-galactosidase (betagal), we previously reported (Song et al, J Exp Med 1997; 186: 1247-1256) that immunization of mice with a single injection of DCs genetically modified with an adenovirus vector expressing betagal confers potent protection against a lethal intravenous tumor challenge, as well as suppression of pre-established lung tumors, resulting in a significant survival advantage. In the present study, we have addressed the question: how long does the memory of tumor antigen- specific immunity persists after DC priming in vivo using this genetically modified DC-based cancer vaccination strategy? To accomplish this, two groups of mice were evaluated: (1) mice surviving >400 days following protection from an initial intravenous tumor challenge after immunization with DC genetically modified to express betagal; and (2) mice surviving >300 days that had previously demonstrated regression of pre-established lung tumors after treatment with DC immunization. By analyzing the antigen-specific cytotoxic T lymphocyte response and challenging these long-term survival mice with a second subcutaneous tumor administration, the data demonstrate that a single administration of DC genetically modified to express a model antigen induces long-lasting, antigen-specific antitumor immunity in both naive and tumor-bearing hosts, observations that have important implications in the development of genetically modified DC-based antitumor vaccination strategies. Gene Therapy (2000) 7, 2080-2086.
树突状细胞（DC）是强大的抗原呈递细胞，在细胞免疫反应的启动中发挥关键作用。我们先前利用表达模型肿瘤抗原β-半乳糖苷酶（βgal）的BALB/c同基因结肠癌细胞系报道（Song等人，《实验医学杂志》1997年；186：1247 - 1256），用表达βgal的腺病毒载体基因修饰的DC单次注射免疫小鼠，可有效保护小鼠免受致死性静脉内肿瘤攻击，并抑制已形成的肺肿瘤，从而带来显著的生存优势。在本研究中，我们探讨了以下问题：使用这种基于基因修饰DC的癌症疫苗接种策略在体内用DC启动后，肿瘤抗原特异性免疫的记忆能持续多久？为实现这一目的，评估了两组小鼠：（1）在用表达βgal的基因修饰DC免疫后，经初次静脉内肿瘤攻击获得保护且存活超过400天的小鼠；（2）在用DC免疫治疗后先前已证明已形成的肺肿瘤消退且存活超过300天的小鼠。通过分析抗原特异性细胞毒性T淋巴细胞反应，并对这些长期存活的小鼠进行第二次皮下肿瘤接种挑战，数据表明，单次给予表达模型抗原的基因修饰DC可在未接触过抗原的和荷瘤宿主中诱导持久的、抗原特异性抗肿瘤免疫，这些观察结果对基于基因修饰DC的抗肿瘤疫苗接种策略的开发具有重要意义。《基因治疗》（2000年）7卷，2080 - 2086页。
