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, CpGoligonucleotide 1826 (CpG ODN). Mice treated with OVA-encapsulated CPTEG:CPH particles elicited the highest CD8+ T cell responses on day 14 and day 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 IgG1 antibody responses in mice serum 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.

Biodegradable particles as vaccine antigen delivery systems for stimulating cellular immune responses

“…adapted from . 58 Downloaded by [National Pingtung University of Science and Technology] at 18:06 03 February 2015 oral/nasal influenza and cancer vaccine carriers, however, the route of administration and formulation characteristics must be carefully considered prior to testing and use. All three polymers have shown enough promise as vaccine vectors to warrant further preclinical and translational studies with a particular focus on diseases requiring Th1-biased immune responses.…”

“…We therefore recently explored this possibility in the context of a well established tumor model system in mice. 58 It was found that vaccination (prime plus boost) with 50:50 CPTEG:CPH particles encapsulating a model tumor Ag, ovalbumin (OVA), provided enhanced protection from subsequent OVA-expressing tumor challenge over other formulations which included: (1) particles encapsulating both OVA and CpG ODN, (2) solution of OVA and CpG ODN, and (3) particles encapsulating OVA plus soluble CpG ODN. Unlike the situation with PLGA particles, co-encapsulation of CpG-ODN reduced rather than enhanced the immunogenicity of the encapsulated Ag (Fig.…”

The effect of polyanhydride chemistry in particle-based cancer vaccines on the magnitude of the anti-tumor immune response

“…On day 35, mice were subcutaneously challenged with tumor cells (see below) and the tumor growth was monitored over time. In this study, blank particles made of polyanhydride copolymer alone (i.e., no antigen) were not used as a control group since they have already been tested in a previous study and did not stimulate any detectable immune responses (since OVA is not an integral part of those particles), nor did they provide any prophylactic protection to the mice challenged with tumor cells [51]. …”

“…CpG ODN has been reported to promote T helper cell type-1 (Th1) immune response [14, 50]. However, Joshi et al found that the co-delivery of CpG ODN and OVA in 50:50 CPTEG:CPH particles did not promote Th1 immune responses [51], which was attributed to observations that 50:50 CPTEG:CPH copolymer activates dendritic cells in a similar fashion to lipopolysaccharide [45], which has been previously reported to abrogate the function of CpG ODN [52]. This finding was further investigated in this research to deduce whether this apparent abrogation of CpG ODN function is specific to the 50:50 CPTEG:CPH copolymer or instead is a possible universal characteristic of polyanhydride copolymers.…”

Nanoparticles in Vaccine Delivery

“…Nanoparticles also offer the potential to protect antigens and adjuvant from premature enzymatic and proteolytic degradation. Nanoparticle delivery systems offer the added strength of multi-component loading which is of considerable significance particularly in immunotherapy where simultaneous delivery of antigens, immunoadjuvants, and targeting ligands is ideal [1][2][3][4][5][6][7][8]. Additionally, due to their large surface area, nanoparticles can be readily surface-engineered with proteins, peptides, polymers, cell-penetrating moieties, reporter groups, and other functional and targeting ligands.…”