Abstract
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 in vivo prophylactic effect. The lipidation approaches (C16-R848 and C16-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+ 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.
Highlights
The use of peptide epitope-based cancer vaccines to activate tumor-associated antigen (TAA)specific T cell responses is an attractive option for generating long-term anti-cancer immune protection because of the ease of synthesis, tolerability, and low risk of adverse effects (Nabel, 2013; Skwarczynski and Toth, 2016; Kumai et al, 2017)
polymer–lipid hybrid nanoparticles (PLNs) were prepared by the nanoprecipitation method and formulated with C16R848 and/or C16SIL to result in four different groups: (i) empty-NP, (ii) NP-C16R848, (iii) NP-C16SIL, and NP-C16SIL-C16R848
We found that the elevated temperature of aqueous phase could effectively reduce viscosity during addition of the organic portion, which resulted in desired encapsulation efficacy (EE) and spherical form under transmission electron microscopy (TEM) (Supplementary Figure S7)
Summary
The use of peptide epitope-based cancer vaccines to activate tumor-associated antigen (TAA)specific T cell responses is an attractive option for generating long-term anti-cancer immune protection because of the ease of synthesis, tolerability, and low risk of adverse effects (Nabel, 2013; Skwarczynski and Toth, 2016; Kumai et al, 2017). TAA-based subunit vaccines are known to be poorly immunogenic, and require potent adjuvants to augment antigen-presenting cell (APC) activation and TAA presentation (Perrie et al, 2008; Coffman et al, 2010; Reed et al, 2013). Among various cancer vaccine adjuvants, TLR7/8 agonists are of particular interest because of their strong activation of APCs (Napolitani et al, 2005), initiation of cross-priming, promotion
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
