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Self-assembled microparticle hydrogel scaffolds to construct artificial tertiary lymphoids for enhanced CAR-T cell
Qiaofeng Li1, Zhisheng Xiao1, Bo Liu1
1Institute of Functional Nano and Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu, 215123, China.
Biomaterials
|January 11, 2026
Summary
Injectable hydrogel microparticles create artificial tertiary lymphoid structures (TLSs) to enhance CAR-T cell therapy for solid tumors. This novel approach improves T-cell function and shows significant therapeutic effects against local and distant tumors.
Area of Science:
- Immunology
- Biomaterials Science
- Oncology
Background:
- Chimeric antigen receptor (CAR)-T cell therapy shows promise for hematologic cancers but struggles with solid tumors.
- Limited immune cell infiltration and inefficient cell-cell interactions within solid tumors hinder CAR-T efficacy.
- Developing strategies to enhance the tumor microenvironment is crucial for improving CAR-T cell therapy in solid tumors.
Purpose of the Study:
- To develop an injectable scaffold mimicking tertiary lymphoid structures (TLSs) to improve CAR-T cell therapy for solid tumors.
- To enhance intratumoral immune cell interactions and T-cell activation and expansion.
- To evaluate the therapeutic efficacy of artificial TLSs against local and distant solid tumors.
Main Methods:
- Fabrication of injectable hydrogel microparticles (HMPs) with opposite charges to form artificial TLSs.
- Encapsulation of immune-stimulating cytokines within HMPs and loading of T cells and B cells into the scaffold.
- Intratumoral injection of artificial TLSs in preclinical solid tumor models.
Main Results:
- The artificial TLSs effectively served as a depot for immunostimulants and promoted B and T lymphocyte interactions.
- Intratumoral injection of CAR-T cells and B cells within the artificial TLSs led to continuous T-cell expansion and activation.
- Significant suppression of local tumors and remarkable abscopal effects on distant tumors were observed.
- Therapeutic performance was greatly enhanced compared to conventional CAR-T therapy.
Conclusions:
- Injectable artificial TLSs represent a novel strategy to overcome challenges in CAR-T cell therapy for solid tumors.
- This approach enhances T-cell efficacy by improving immune cell infiltration and interaction within the tumor microenvironment.
- The developed artificial TLSs demonstrate significant potential for improving treatment outcomes in solid tumor patients.
