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Engineered polymer-based scaffold as an implantable therapeutic vaccine against melanoma
Authors:Anjana Unnikrishnan  Meera Menon  Gopika K. G.  Reba Elsa Sam  Manzoor Koyakutty  Anusha Ashokan
Affiliation:1. Thanmatra Innovations Private Limited, Kochi, Kerala, India

Contribution: ​Investigation (supporting), Methodology (equal), Project administration (supporting), Writing - original draft (supporting);2. Department of Biotechnology, Cochin University of Science and Technology, Kochi, Kerala, India

Contribution: Formal analysis (equal), ​Investigation (supporting), Methodology (supporting), Project administration (supporting), Validation (supporting), Writing - original draft (supporting), Writing - review & editing (supporting);3. Thanmatra Innovations Private Limited, Kochi, Kerala, India

Contribution: ​Investigation (supporting), Methodology (supporting);4. Department of Biotechnology, Cochin University of Science and Technology, Kochi, Kerala, India

Contribution: Formal analysis (supporting), ​Investigation (supporting), Methodology (supporting);5. Thanmatra Innovations Private Limited, Kochi, Kerala, India

Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India

Contribution: Supervision (supporting);6. Thanmatra Innovations Private Limited, Kochi, Kerala, India

Abstract:Although tumor-antigen-based therapeutic cancer vaccines are a potential cancer immunotherapy strategy, recent clinical trials show low efficacy for multiple reasons. One method that has been recently investigated to improve the efficacy of therapeutic cancer vaccines is the development of implantable vaccines for sustained delivery of antigens and CD8 T cell activation. Here, we optimized the composition for an implantable vaccine scaffold composed of alginate, polyvinyl alcohol, and poly(methyl vinyl ether- alt-maleic anhydride) loaded with tumor antigens. Considering the adjuvant property of aluminum compounds, aluminum ion was used to crosslink alginate in the scaffold. The scaffold showed an effective antigen incorporation efficiency of 90.34 ± 0.55% using ovalbumin as the model antigen and 89.67 ± 2.8% using B16-F10 cell lysate. SEM analysis of the scaffold showed pore size ranging from 5 to 10 μm. Cell viability analysis using mouse RAW 264.7 macrophages proved the cytocompatibility of the scaffold. In vitro antigen release studies using ovalbumin showed 8.42% release for a period of 14 days. In vivo antitumor analysis carried out in subcutaneous mouse B16-F10 melanoma model demonstrated that the scaffold vaccine reduced the rate of tumor growth and improved survival in tested animals. The median survival time increased from 29 days in untreated animals to 58 days in scaffold vaccine-implanted animals.
Keywords:cancer immunotherapy  implantable Vaccine  scaffold vaccine  therapeutic cancer vaccine     B16-F10 melanoma model
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