- Poster presentation
- Open Access
Chitosan thermogels for local T lymphocyte delivery for cancer immunotherapy
© Monette et al. 2015
Published: 4 November 2015
The success of systemic adoptive T cell transfer lies in the capacity of the antigen-experienced cytotoxic T lymphocytes to access and persist within the tumour microenvironment. The mimicking of tertiary lymphoid structures that promote a protective immune response against cancer can be achieved using an injectable biocompatible matrix that releases anti-tumour, proliferating T lymphocytes. Prime candidates for this application are liquid, chitosan-based, biocompatible thermogels which rapidly gelify at physiological temperatures. Therefore, we aimed to fine-tune an injectable chitosan-based thermogel formulation that would provide an environment permitting the three-dimensional proliferation and release of T lymphocytes whose activation state can be influenced by the surrounding conditions. We have developed a novel chitosan formulation that is both cytocompatible and injectable, and which has ideal mechanical properties and porosity for T cell encapsulation and growth. With such promising characteristics, we hypothesize that the injection of these T lymphocytes loaded hydrogels into the tumour microenvironment will provide a means for a continuous delivery of T lymphocytes towards the reprogramming of inflammation mechanisms and the reduction of tumour burden.
Materials and methods
Novel T cell cytocompatible chitosan thermogels were prepared using combinations of gelling agents. Their rheological properties, mechanical strengths, pH, osmolality, and morphology were evaluated. Three formulations were selected for human T cell encapsulation. Biocompatibility was assessed using live/dead staining and fluorescent microscopy. Thermogel- and supernatant-derived T cells and tumour infiltrating lymphocytes were immunophenotyped over time using flow cytometry.
Results and conclusions
We have optimized thermogel formulations supporting the encapsulation of T lymphocytes in vitro. Use of flow cytometry and microscopy demonstrates which novel thermogel formulation is best suited for cell viability, proliferation, and escape over time, along with the maintenance of T lymphocytes cellular phenotype and an activation status that can be influenced by surrounding conditions. Our injectable three-dimensional T lymphocyte cultures may serve to complement current adoptive cell transfer immunotherapies.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.