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Bio‐Hybrid Tumor Cell‐Templated Capsules: A Generic Formulation Strategy for Tumor Associated Antigens in View of Immune Therapy
Authors:Lien Lybaert  Elly De Vlieghere  Riet De Rycke  Nane Vanparijs  Olivier De Wever  Stefaan De Koker  Bruno G. De Geest
Affiliation:1. Department of Pharmaceutics, Ghent University, Ghent, Belgium;2. Laboratory of Experimental Cancer Research, Ghent University, Ghent, Belgium;3. Department of Biomedical Molecular Biology IRC, Ghent University, Zwijnaarde, Belgium;4. Department of Molecular Biomedical Research VIB, Ghent University, Zwijnaarde, Belgium
Abstract:For the development of effective anti‐cancer vaccines, tumor associated antigens need to be internalized by antigen presenting cells alongside specific co‐stimulatory signals. Interestingly, relative to soluble antigens, nano‐ and micro‐particulate antigens are much better presented to CD8 T cells, a crucial step in the induction of cytotoxic T cells that can eliminate malignant cells. In this regard, a generic strategy to encapsulate cancer cell derived proteins into a particulate delivery system would be of high interest. Here we present a versatile approach to incorporate cancer cell proteins into polymeric capsules using the cells themselves as templates for layer‐by‐layer assembly of complimentary interacting species. After coating, the cells are killed by hypo‐osmotic treatment leading to bio‐hybrid capsules loaded with cell lysate. Particular focus is devoted in this work on choosing the optimal coating components and conditions to maximize cell membrane integrity during the coating process, minimize pre‐mature protein release and achieve optimal encapsulation of cell lysate upon lysis of the cells. To further underline the generic nature of our approach, we demonstrate that heat shock proteins, important immune‐activators, can be induced and encapsulated into the bio‐hybrid capsules.
Keywords:Layer‐by‐layer  single cell encapsulation  cancer vaccination
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