The Sidney Kimmel Cancer Center and the Skip Viragh Pancreatic Cancer Center at Johns Hopkins, Baltimore, MD, USA.
Semin Oncol. 2012 Jun;39(3):311-22. doi: 10.1053/j.seminoncol.2012.02.008.
Active immunotherapy targeting dendritic cells (DCs) has shown great promise in preclinical models and in human clinical trials for the treatment of malignant disease. Sipuleucel-T (Provenge, Dendreon, Seattle, WA), which consists of antigen-loaded dendritic cells (DCs), recently became the first targeted therapeutic cancer vaccine to be approved by the US Food and Drug Administration (FDA). However, ex vivo therapies such as Provenge have practical limitations and elicit an immune response with limited scope. By contrast, live-attenuated Listeria monocytogenes (Lm) naturally targets DCs in vivo and stimulates both innate and adaptive cellular immunity. Lm-based vaccines engineered to express cancer antigens have demonstrated striking efficacy in several animal models and have resulted in encouraging anecdotal survival benefit in early human clinical trials. Two different Lm-based vaccine platforms have advanced into phase II clinical trials in cervical and pancreatic cancer. Future Lm-based clinical vaccine candidates are expected to feature polyvalent antigen expression and to be used in combination with other immunotherapies or conventional therapies such as radiotherapy and chemotherapy to augment efficacy.
针对树突状细胞 (DC) 的主动免疫疗法在恶性疾病的临床前模型和人类临床试验中显示出巨大的潜力。Sipuleucel-T（Provenge，Dendreon，西雅图，华盛顿州）由负载抗原的树突状细胞 (DC) 组成，最近成为第一个获得美国食品和药物管理局 (FDA) 批准的靶向治疗癌症疫苗。然而，Provenge 等体外疗法存在实际限制，并且引发的免疫反应范围有限。相比之下，活减毒李斯特菌 (Lm) 自然靶向体内的树突状细胞，并刺激先天和适应性细胞免疫。表达癌症抗原的基于 Lm 的疫苗在几种动物模型中显示出显著的疗效，并在早期人类临床试验中导致令人鼓舞的生存获益的传闻。两种不同的基于 Lm 的疫苗平台已进入宫颈癌和胰腺癌的 II 期临床试验。未来的基于 Lm 的临床候选疫苗预计将具有多价抗原表达，并与其他免疫疗法或常规疗法（如放疗和化疗）联合使用，以提高疗效。
