Faculty of Pharmacy, University of Coimbra, 3000-548, Coimbra, Portugal.
Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504, Coimbra, Portugal.
J Immunother Cancer. 2019 Sep 4;7(1):238. doi: 10.1186/s40425-019-0716-8.
Dendritic cells (DCs) are central players in the immune system, with an exquisite capacity to initiate and modulate immune responses. These functional characteristics have led to intense research on the development of DC-based immunotherapies, particularly for oncologic diseases. During recent decades, DC-based vaccines have generated very promising results in animal studies, and more than 300 clinical assays have demonstrated the safety profile of this approach. However, clinical data are inconsistent, and clear evidence of meaningful efficacy is still lacking. One of the reasons for this lack of evidence is the limited functional abilities of the used ex vivo-differentiated DCs. Therefore, alternative approaches for targeting and modulating endogenous DC subpopulations have emerged as an attractive concept. Here, we sought to revise the evolution of several strategies for the in situ mobilization and modulation of DCs. The first approaches using chemokine-secreting irradiated tumor cells are addressed, and special attention is given to the cutting-edge injectable bioengineered platforms, programmed to release chemoattractants, tumor antigens and DC maturating agents. Finally, we discuss how our increasing knowledge of DC biology, the use of neoantigens and their combination with immune checkpoint inhibitors can leverage the refinement of these polymeric vaccines to boost their antitumor efficacy.
树突状细胞 (DCs) 是免疫系统的核心参与者,具有启动和调节免疫反应的卓越能力。这些功能特性促使人们对基于 DC 的免疫疗法进行了深入研究,特别是针对肿瘤疾病。在过去几十年中,基于 DC 的疫苗在动物研究中取得了非常有前景的结果,超过 300 项临床研究表明了这种方法的安全性。然而,临床数据并不一致,仍然缺乏有意义疗效的明确证据。造成这种证据不足的原因之一是所使用的体外分化的 DC 功能能力有限。因此,针对内源性 DC 亚群的靶向和调节的替代方法已经成为一个有吸引力的概念。在这里,我们试图回顾几种原位动员和调节 DC 的策略的演变。首先讨论了使用分泌趋化因子的辐照肿瘤细胞的方法,并特别关注了可注射的生物工程平台,这些平台被编程为释放趋化因子、肿瘤抗原和 DC 成熟剂。最后,我们讨论了我们对 DC 生物学的不断了解、新抗原的使用以及它们与免疫检查点抑制剂的结合如何能够提高这些聚合物疫苗的抗肿瘤疗效。