Hernando Juan José, Park Tjoung-Won, Kuhn Walther C
Department of Obstetrics and Gynaecology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Anticancer Res. 2003 Sep-Oct;23(5b):4293-303.
Major advances in understanding the functional interactions between tumour cells and the host immune system, in particular the generation and regulation of T cell immunity, have revived interest in cancer vaccination strategies. A crucial step for mounting an anti-tumour response is the capture, processing and presentation of tumour antigens (TA) to cognate T cells by professional antigen-presenting cells (APC), followed by their activation and clonal proliferation. Dendritic cells (DC) are potent APC with the unique ability to stimulate primary immune responses. Animal models have demonstrated that TA-charged DC can activate specific cytotoxic T cells (CTL) and even regression of established tumours in cancer-bearing hosts. These findings, as well as the elaboration of methods for generating large numbers of DC ex vivo, have provided a compelling rationale for using DC as potent adjuvants to deliver TA to the immune system in order to trigger or amplify an inadequate response. The capacity of TA-pulsed DC to induce significant CTL immunity translating into occasional therapeutic benefit has been documented in several clinical settings including B cell lymphoma, myeloma, melanoma, prostate, colon, ovarian and renal cell carcinoma. In this review, we summarize key biological functions of DC and focus on recent DC-based vaccination trials of breast, ovarian and cervical cancer.
在理解肿瘤细胞与宿主免疫系统之间的功能相互作用,尤其是T细胞免疫的产生和调节方面取得的重大进展,重新激发了人们对癌症疫苗接种策略的兴趣。启动抗肿瘤反应的关键步骤是专职抗原呈递细胞(APC)捕获、处理肿瘤抗原(TA)并将其呈递给同源T细胞,随后T细胞被激活并进行克隆增殖。树突状细胞(DC)是强大的APC,具有刺激初始免疫反应的独特能力。动物模型表明,负载TA的DC可以激活特异性细胞毒性T细胞(CTL),甚至使荷瘤宿主中已形成的肿瘤消退。这些发现以及体外大量生成DC方法的完善,为使用DC作为强效佐剂将TA递送至免疫系统以触发或增强不足的免疫反应提供了令人信服的理论依据。在包括B细胞淋巴瘤、骨髓瘤、黑色素瘤、前列腺癌、结肠癌、卵巢癌和肾细胞癌在内的多种临床环境中,已证明TA脉冲DC诱导显著CTL免疫并偶尔产生治疗益处的能力。在本综述中,我们总结了DC 的关键生物学功能,并重点关注近期基于DC的乳腺癌、卵巢癌和宫颈癌疫苗接种试验。