Journal article
Pentaerythritol-based lipid A bolsters the antitumor efficacy of a polyanhydride particle-based cancer vaccine
Nanomedicine, Vol.21, pp.102055-102055
10/2019
DOI: 10.1016/j.nano.2019.102055
PMCID: PMC6814548
PMID: 31319179
Abstract
The primary objective of this study was to enhance the antitumor efficacy of a model cancer vaccine through co-delivery of pentaerythritol lipid A (PELA), an immunological adjuvant, and a model tumor antigen, ovalbumin (OVA), separately loaded into polyanhydride particles (PA). In vitro experiments showed that encapsulation of PELA into PA (PA-PELA) significantly enhanced its stimulatory capacity on dendritic cells as evidenced by increased levels of the cell surface costimulatory molecules, CD80/CD86. In vivo experiments showed that PA-PELA, in combination with OVA-loaded PA (PA-OVA), significantly expanded the OVA-specific CD8+ T lymphocyte population compared to PA-OVA alone. Furthermore, OVA-specific serum antibody titers of mice vaccinated with PA-OVA/PA-PELA displayed a significantly stronger shift toward a Th1-biased immune response compared to PA-OVA alone, as evidenced by the substantially higher IgG2C:IgG1 ratios achieved by the former. Analysis of E.G7-OVA tumor growth curves showed that mice vaccinated with PA-OVA/PA-PELA had the slowest average tumor growth rate.
The study indicated that the immunostimulatory effect of PELA on DCs was significantly improved upon encapsulation into PA particles. The study also demonstrated that incorporation of PELA significantly enhanced the immunogenicity of PA particle-based cancer vaccines, as indicated by significantly increased levels of OVA-specific CD8+ T cells, and skewed the immune response toward a Th1 phenotype. Furthermore, the PELA containing formulation, when used in combination with PA-OVA, demonstrated a significant decrease in the rate of tumor progression when compared to PA-OVA alone. Taken together, these results emphasize the potential for PA-PELA to be utilized as an immunological adjuvant in cancer vaccines. [Display omitted]
Details
- Title: Subtitle
- Pentaerythritol-based lipid A bolsters the antitumor efficacy of a polyanhydride particle-based cancer vaccine
- Creators
- Emad I Wafa - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USASean M Geary - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USAKathleen A Ross - Department of Chemical and Biological Engineering, College of Engineering, Iowa State University, Ames, IA, USAJonathan T Goodman - Department of Chemical and Biological Engineering, College of Engineering, Iowa State University, Ames, IA, USABalaji Narasimhan - Department of Chemical and Biological Engineering, College of Engineering, Iowa State University, Ames, IA, USAAliasger K Salem - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Nanomedicine, Vol.21, pp.102055-102055
- DOI
- 10.1016/j.nano.2019.102055
- PMID
- 31319179
- PMCID
- PMC6814548
- NLM abbreviation
- Nanomedicine
- ISSN
- 1549-9634
- eISSN
- 1549-9642
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 10/2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9984216673002771
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