Hydrogel-infused dendritic cells for anticancer immunotherapy
A new technique that polymerizes cellular cytosol with hydrogel generates robust biomimetic antigen presenting systems for anticancer adoptive T cell therapy.
Adoptive T cell therapy that extracts, expands, and reinfuses endogenous T cells from patents’ body is an emerging therapeutic regimen that has demonstrated compelling therapeutic benefits against cancer and chronic viral infections. A critical component of this therapy lies in an effective antigen presenting system for T cell expansion, and the common adoption of live dendritic cells is encumbered by maintenance and logistics requirements. Dr. Che-Ming Jack Hu and his research team at the Institute of Biomedical Sciences (IBMS), Academia Sinica (AS) developed a novel technique to transform live dendritic cells into robust and modular antigen-presenting biomaterials that can be freeze-dried and stored in powderized form but retain cell-like properties for effective T cell activation. Dr. Hu’s team devised a non-disruptive intracellular hydrogelation approach, in which a biocompatible hydrogel monomer and a photo-initiator were first introduced into cellular cytosol through direct diffusion. The resulting cells were then treated with UV light to activate radical polymerization of the hydrogel, generating a cell-gel hybrid construct that carries cellular components on its surface and exhibits extraordinary stability for storage and utility. The entire gelation process can be completed within 10 minutes and is highly scalable.
The research team demonstrated multiple features of the gelated dendritic cells, including the ability to load peptide antigens of choice, functionalization with delivery carriers with synergistic cytokine delivery, and robust antigen-specific T cell expansion. The system was able to enhance adoptive T cell therapy in a mouse tumor model, leading to suppressed tumor growth, prolonged survival, and increased population of tumor infiltrating lymphocytes. The team suggests that this new class of biomaterial can open up new opportunities in the field of immunoengineering research and immunological interrogation.
The study entitled “Facile transformation of murine and human primary dendritic cells into robust and modular artificial antigen-presenting systems by intracellular hydrogelation” was published online in Advanced Materials on the 7th of June (https://onlinelibrary.wiley.com/doi/10.1002/adma.202101190). The research team is led by first author Dr. Jung-Chen Lin and corresponding author Dr. Che-Ming Jack Hu at IBMS. The work is a collaborative effort with Dr. Hui-Wen Chen at the Department of Veterinary Medicine of National Taiwan University and Dr. Tong-Young Lee at Celtech Inc. The study is funded by the Academia Sinica Career Development Award and the Excellent Young Scholars Award from the Ministry of Science and Technology, Taiwan.