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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.