Injectable Biomimetic Hydrogels as Tools for Efficient T Cell Expansion and Delivery

Area of Science:

• Biomaterials Science
• Immunology
• Cancer Therapy

Background:

• Biomaterial scaffolds offer controlled immunomodulation and spatiotemporal control of immune cues.
• Adoptive T cell transfer efficacy relies on tumor-specific T cell localization and persistence.
• Polyisocyanopeptide (PIC) hydrogels are injectable, thermo-responsive polymeric scaffolds.

Purpose of the Study:

• To explore synthetic PIC hydrogels for in vitro T cell expansion and in vivo local delivery.
• To evaluate PIC hydrogels as 3D culture systems for adoptive T cell therapy.
• To assess the in vivo behavior and immunogenicity of PIC hydrogels for cell delivery.

Main Methods:

• Investigated PIC hydrogel properties for T cell culture and injection.
• Assessed in vitro T cell survival and expansion within PIC hydrogels.
• Evaluated in vivo gelation, localization, cell release, and inflammatory response after subcutaneous injection.

Main Results:

• PIC hydrogels supported robust in vitro T cell survival and expansion, facilitating cell recovery.
• Injected PIC hydrogels formed stable, localized 3D structures in vivo for at least 4 weeks.
• Co-delivered cells gradually egressed from the gel and migrated to distant organs, with no observed inflammation.

Conclusions:

• PIC hydrogels are effective for in vitro T cell expansion and in vivo local delivery.
• Their thermo-responsive and non-immunogenic nature makes them suitable for adoptive T cell therapy.
• Functionalization of PIC polymers allows for steering cell phenotype and response, improving cancer immunotherapy strategies.