AUTHOR=Wang Junqing , Zope Harshal , Islam Mohammad Ariful , Rice Jamie , Dodman Sage , Lipert Kevin , Chen Yunhan , Zetter Bruce R. , Shi Jinjun 

TITLE=Lipidation Approaches Potentiate Adjuvant-Pulsed Immune Surveillance: A Design Rationale for Cancer Nanovaccine

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2020.00787

DOI=10.3389/fbioe.2020.00787

ISSN=2296-4185

ABSTRACT=<p>Adjuvant-pulsed peptide vaccines hold great promise for the prevention and treatment of different diseases including cancer. However, it has been difficult to maximize vaccine efficacy due to numerous obstacles including the unfavorable tolerability profile of adjuvants, instability of peptide antigens, limited cellular uptake, and fast diffusion from the injection site, as well as systemic adverse effects. Here we describe a robust lipidation approach for effective nanoparticle co-delivery of low-molecular weight immunomodulators (TLR7/8 agonists) and peptides (SIINFEKL) with a potent <italic>in vivo</italic> prophylactic effect. The lipidation approaches (C<sub>16</sub>-R848 and C<sub>16</sub>-SIINFEKL) increased their hydrophobicity that is intended not only to improve drug encapsulation efficiency but also to facilitate the membrane association, intracellular trafficking, and subcellular localization. The polymer–lipid hybrid nanoparticles (PLNs) are designed to sustain antigen/adjuvant levels with less systemic exposure. Our results demonstrated that a lipidated nanovaccine can induce effective immunity by enhancing the expansion and activation of antigen-specific CD8<sup>+</sup> T cells. This adaptive immune response led to substantial tumor suppression with improved overall survival in a prophylactic setting. Our new methodology enhances the potential of nanovaccines for anti-tumor therapy.</p>