Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Mol Immunol. 2018 Jun;98:8-12. doi: 10.1016/j.molimm.2017.11.001. Epub 2017 Nov 8.
Cancer immunotherapy has gained much attention for next-generation cancer treatment. To conduct cancer immunotherapy, efficient antigen delivery systems must be able to deliver an antigen selectively to antigen-presenting cells, release it at suitable sites for induction of cross-presentation, and simultaneously induce activation of immunocompetent cells. Liposomes are a candidate for use as such multifunctional antigen delivery carriers because of their capability for easy functionalization. This review describes the rational design of liposome-based antigen delivery systems. Surface modification of liposomes by pH-responsive or fusogenic materials can achieve cytoplasmic delivery of antigen, leading to cross-presentation of exogenous antigen via a "cytosolic pathway." In contrast, targeting surface receptors on antigen presenting cells or the selective release of antigen in early endosome induced "vacuolar pathway"-mediated cross-presentation. Introduction of adjuvant molecules such as Toll like receptor agonists, synthetic cationic lipids or bioactive polysaccharides to liposomes improved their immunity-inducing ability. Combination with cancelling systems of immunosuppression in tumor microenvironment enhanced antitumor immunity of antigen delivery systems. Further understanding of immunity-inducing mechanism and molecular basis of tumor immunosuppressive environments and purposeful design of liposome-based antigen delivery systems can provide effective immunity-inducing systems for cancer immunotherapy.
癌症免疫疗法在下一代癌症治疗中受到了广泛关注。为了进行癌症免疫治疗，高效的抗原递药系统必须能够将抗原选择性递送至抗原呈递细胞，在合适的部位释放以诱导交叉呈递，并同时诱导免疫活性细胞的激活。由于其易于功能化的能力，脂质体是作为这种多功能抗原递药载体的候选物。本文综述了基于脂质体的抗原递药系统的合理设计。通过 pH 响应性或融合材料对脂质体进行表面修饰，可以实现抗原的细胞质递送，从而通过“细胞质途径”对外源抗原进行交叉呈递。相比之下，靶向抗原呈递细胞上的表面受体或在早期内体中选择性释放抗原可诱导“空泡途径”介导的交叉呈递。将佐剂分子（如 Toll 样受体激动剂、合成阳离子脂质或生物活性多糖）引入脂质体可以提高其免疫诱导能力。与肿瘤微环境中免疫抑制系统的联合使用增强了抗原递药系统的抗肿瘤免疫。进一步了解免疫诱导机制和肿瘤免疫抑制环境的分子基础，并进行有针对性的基于脂质体的抗原递药系统设计，可以为癌症免疫治疗提供有效的免疫诱导系统。
