Nam Jutaek, Son Sejin, Park Kyung Soo, Moon James J
Department of Pharmaceutical Sciences Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA.
Department of Biomedical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA.
Adv Sci (Weinh). 2021 Jan 6;8(5):2002577. doi: 10.1002/advs.202002577. eCollection 2021 Mar.
Nanoparticles (NPs) can serve as a promising vaccine delivery platform for improving pharmacological property and codelivery of antigens and adjuvants. However, NP-based vaccines are generally associated with complex synthesis and postmodification procedures, which pose technical and manufacturing challenges for tailor-made vaccine production. Here, modularly programmed, polyethyleneimine (PEI)-based NP vaccines are reported for simple production of personalized cancer vaccines. Briefly, PEI is conjugated with neoantigens by facile coupling chemistry, followed by electrostatic assembly with CpG adjuvants, leading to the self-assembly of nontoxic, sub-50 nm PEI NPs. Importantly, PEI NPs promote activation and antigen cross-presentation of antigen-presenting cells and cross-priming of neoantigen-specific CD8 T cells. Surprisingly, after only a single intratumoral injection, PEI NPs with optimal PEGylation elicit as high as ≈30% neoantigen-specific CD8 T cell response in the systemic circulation and sustain elevated CD8 T cell response over 3 weeks. PEI-based nanovaccines exert potent antitumor efficacy against pre-established local tumors as well as highly aggressive metastatic tumors. PEI engineering for modular incorporation of neoantigens and adjuvants offers a promising strategy for rapid and facile production of personalized cancer vaccines.
纳米颗粒（NPs）可作为一种很有前景的疫苗递送平台，用于改善药理学特性以及抗原和佐剂的共递送。然而，基于NP的疫苗通常与复杂的合成和后修饰程序相关，这给定制疫苗生产带来了技术和制造方面的挑战。在此，报道了模块化编程的基于聚乙烯亚胺（PEI）的NP疫苗，用于简单生产个性化癌症疫苗。简而言之，PEI通过简便的偶联化学与新抗原共轭，随后与CpG佐剂进行静电组装，导致无毒的亚50 nm PEI NPs自组装。重要的是，PEI NPs促进抗原呈递细胞的活化和抗原交叉呈递以及新抗原特异性CD8 T细胞的交叉启动。令人惊讶的是，仅进行一次瘤内注射后，具有最佳聚乙二醇化的PEI NPs在全身循环中引发高达约30%的新抗原特异性CD8 T细胞反应，并在3周内维持升高的CD8 T细胞反应。基于PEI的纳米疫苗对预先建立的局部肿瘤以及高度侵袭性的转移性肿瘤具有强大的抗肿瘤功效。用于模块化掺入新抗原和佐剂的PEI工程为快速简便地生产个性化癌症疫苗提供了一种有前景的策略。
