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Chitosan thermogels for local expansion and delivery of tumor-specific T lymphocytes towards enhanced cancer immunotherapies

Paper ID Volume ID Publish Year Pages File Format Full-Text
5511 394 2016 13 PDF Available
Title
Chitosan thermogels for local expansion and delivery of tumor-specific T lymphocytes towards enhanced cancer immunotherapies
Abstract

The success of promising anti-cancer adoptive cell therapies relies on the abilities of the perfused CD8+ T lymphocytes to gain access to and persist within the tumor microenvironment to carry out their cytotoxic functions. We propose a new method for their local delivery as a living concentrate, which may not only reduce the numbers of cells required for treatment but also enhance their site-specific mobilization. Using combinations of sodium hydrogen carbonate and phosphate buffer as gelling agents, novel injectable chitosan-based biocompatible thermogels (CTGels) having excellent mechanical properties and cytocompatibility have been developed. Three thermogel formulations with acceptable physicochemical properties, such as physiological pH and osmolality, macroporosity, and gelation rates were compared. The CTGel2 formulation outperformed the others by providing an environment suitable for the encapsulation of viable CD8+ T lymphocytes, supporting their proliferation and gradual release. In addition, the encapsulated T cell phenotypes were influenced by surrounding conditions and by tumor cells, while maintaining their capacity to kill tumor cells. This strongly suggests that cells encapsulated in this formulation retain their anti-cancer functions, and that this locally injectable hydrogel may be further developed to complement a wide variety of existing immunotherapies.

Keywords
Cancer; Immunotherapy; T lymphocytes; Chitosan; Hydrogel; Injectable
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Chitosan thermogels for local expansion and delivery of tumor-specific T lymphocytes towards enhanced cancer immunotherapies
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 75, January 2016, Pages 237–249
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us