Enhancement of Anti-Tumor Effect of Particulate Vaccine Delivery System by ‘Bacteriomimetic’ CpG Functionalization of Poly-Lactic-Co-glycolic Acid Nanoparticles

Abstract

Aim: Low immunogenicity remains a major obstacle in realizing the full potential of cancer vaccines. In this study, we evaluated CpG-coated tumor antigen (Tag)-encapsulating ‘bacteriomimetic’ nanoparticles (CpG-nanoparticle [NP]-Tag NPs) as an approach to enhance anti-tumor immunity. Materials & methods: CpG-NP-Tag NPs were synthesized, characterized for their physicochemical properties and tested in vivo.Results: We found CpG predosing followed by intraperitoneal (IP) immunization with CpG-NP-Tag NPs significantly attenuated tumor growth in female BALB/c mice compared with respective controls. Histopathological and Immunofluorescence data revealed CpG-NP-Tag tumors had lower proliferation, higher apoptotic activity, greater CD4⁺ and CD8⁺ T cell infiltration as well as higher IFN-γ levels as compared with control groups. Conclusion: Our findings suggest CpG-NP-Tag NPs can enhance anti-tumor effect of nanoparticulate tumor vaccination system.

Keywords::

• antigen
• breast cancer
• immunotherapy
• nanoparticle
• NP
• vaccines

Acknowledgements

We would like to thank Xiangle Sun from core facility, and Alakananda Basu, Dong-Ming Su and Ryan Rich for their technical help.

Financial & competing interests disclosure

This research was supported in part by National Institute on Minority Health and Health Disparities Grant 1P20 MD006882 (to JK Vishwanatha), Department of Molecular and Medical Genetics at UNTHSC and Predoctoral Fellowship (BC093521) from DOD Breast Cancer Research Program (SI Thamake). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This research was supported in part by National Institute on Minority Health and Health Disparities Grant 1P20 MD006882 (to JK Vishwanatha), Department of Molecular and Medical Genetics at UNTHSC and Predoctoral Fellowship (BC093521) from DOD Breast Cancer Research Program (SI Thamake). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.