Modularly Programmable Nanoparticle Vaccine Based on Polyethyleneimine for Personalized Cancer Immunotherapy

Advanced Science

Kyung Soo Park¹  Jutaek Nam²  Sejin Son²  James J. Moon³ 

[1] Department of Biomedical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA;Department of Pharmaceutical Sciences Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA;Department of Pharmaceutical Sciences Department of Biomedical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA;

关键词: cancer vaccines;    immunotherapy;    nanoparticles;    neoantigens;   

DOI  :  10.1002/advs.202002577

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown