title: Characterizing the antitumor response in mice treated with antigen-loaded polyanhydride microparticles.
abstract: Delivery of vaccine antigens with an appropriate adjuvant can trigger potential immune responses against cancer leading to reduced tumor growth and improved survival. In this study, various formulations of a bioerodible amphiphilic polyanhydride copolymer based on 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) and 1,6-bis(p-carboxyphenoxy) hexane (CPH) with inherent adjuvant properties were evaluated for antigen-loading properties, immunogenicity and antitumor activity. Mice were vaccinated with 50:50 CPTEG:CPH microparticles encapsulating a model tumor antigen, ovalbumin (OVA), in combination with the Toll-like receptor-9 agonist, CpG oligonucleotide 1826 (CpG ODN). Mice treated with OVA-encapsulated CPTEG:CPH particles elicited the highest CD8(+) T cell responses on days 14 and 20 when compared to other treatment groups. This treatment group also displayed the most delayed tumor progression and the most extended survival times. Particles encapsulating OVA and CpG ODN generated the highest anti-OVA IgG(1) antibody responses in mice but these mice did not show significant tumor protection. These results suggest that antigen-loaded CPTEG:CPH microparticles can stimulate antigen-specific cellular responses and could therefore potentially be used to promote antitumor responses in cancer patients.
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Vijaya B
authors.initials: VB
authors.lastname: Joshi
authors.forename: Sean M
authors.initials: SM
authors.lastname: Geary
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Carrillo-Conde
authors.forename: Balaji
authors.initials: B
authors.lastname: Narasimhan
authors.forename: Aliasger K
authors.initials: AK
authors.lastname: Salem
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology*; D010316:Particle Size; D049388:Polyanhydrides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D055672:Static Electricity; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014611:Vaccination
chemical_list: D000941:Antigens; D000970:Antineoplastic Agents; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D049388:Polyanhydrides; C523504:poly(1,6-bis-4-carboxyphenoxyhexane); C546712:poly(1,8-bis(4-carboxyphenoxy)-3,6-dioxaoctane); D011092:Polyethylene Glycols; D010047:Ovalbumin