Kirk C J, Mulé J J
Department of Surgery, Tumor Immunology Program of the Comprehensive Cancer Center, University of Michigan Medical Center, Ann Arbor 48109-0666, USA.
Hum Gene Ther. 2000 Apr 10;11(6):797-806. doi: 10.1089/10430340050015419.
Dendritic cells (DCs) are potent antigen-presenting cells capable of priming activation of naive T cells. Because of their immunostimulatory capacity, immunization with DCs presenting tumor antigens has been proposed as a treatment regimen for cancer. The results from translational research studies and early clinical trials point to the need for improvement of DC-based tumor vaccines before they become a more broadly applicable treatment modality. In this regard, studies suggest that genetic modification of DCs to express tumor antigens and/or immunomodulatory proteins may improve their capacity to promote an antitumor response. Because the DC phenotype is relatively unstable, nonperturbing methods of gene transfer must be employed that do not compromise viability or immunostimulatory capacity. DCs expressing transgenes encoding tumor antigens have been shown to be more potent primers of antitumor immunity both in vitro and in animal models of disease; in some measures of immune priming, gene-modified DCs exceeded their soluble antigen-pulsed counterparts. Cytokine gene modification of DCs has improved their capacity to prime tumor antigen-specific T cell responses and promote antitumor immunity in vivo. Here, we review the current status of gene-modified DCs in both human and murine studies. Although successful results have been obtained to date in experimental systems, we discuss potential problems that have already arisen and may yet be encountered before gene-modified DCs are more widely applicable for use in human clinical trials.
树突状细胞（DCs）是强大的抗原呈递细胞，能够启动幼稚T细胞的激活。由于其免疫刺激能力，用呈递肿瘤抗原的DCs进行免疫已被提议作为一种癌症治疗方案。转化研究和早期临床试验的结果表明，在基于DC的肿瘤疫苗成为更广泛适用的治疗方式之前，有必要对其进行改进。在这方面，研究表明对DCs进行基因改造以表达肿瘤抗原和/或免疫调节蛋白可能会提高它们促进抗肿瘤反应的能力。由于DC表型相对不稳定，必须采用不干扰基因转移的方法，这些方法不会损害其活力或免疫刺激能力。在体外和疾病动物模型中，表达编码肿瘤抗原转基因的DCs已被证明是更有效的抗肿瘤免疫启动剂；在一些免疫启动指标中，基因改造的DCs超过了其可溶性抗原脉冲对应的DCs。对DCs进行细胞因子基因改造提高了它们启动肿瘤抗原特异性T细胞反应和促进体内抗肿瘤免疫的能力。在这里，我们综述了基因改造DCs在人类和小鼠研究中的现状。尽管迄今为止在实验系统中已经取得了成功的结果，但我们讨论了在基因改造DCs更广泛应用于人类临床试验之前已经出现以及可能会遇到的潜在问题。
