Related Experiment Video
Updated: Jul 27, 2025
Author Spotlight: Advancements in Hypoxia-Sensitive CAR-T Therapy for Enhanced Cancer Immunotherapy
Published on: June 14, 2024
Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR
Angela Q Zhang1,2,3, Alexander Hostetler1,4, Laura E Chen1,4
1Koch Institute for Integrative Cancer Research, Cambridge, MA, USA.
Abstract:
The effectiveness of chimaeric antigen receptor (CAR) T cell therapies for solid tumours is hindered by difficulties in the selection of an effective target antigen, owing to the heterogeneous expression of tumour antigens and to target antigen expression in healthy tissues. Here we show that T cells with a CAR specific for fluorescein isothiocyanate (FITC) can be directed against solid tumours via the intratumoural administration of a FITC-conjugated lipid-poly(ethylene)-glycol amphiphile that inserts itself into cell membranes. In syngeneic and human tumour xenografts in mice, 'amphiphile tagging' of tumour cells drove tumour regression via the proliferation and accumulation of FITC-specific CAR T cells in the tumours. In syngeneic tumours, the therapy induced the infiltration of host T cells, elicited endogenous tumour-specific T cell priming and led to activity against distal untreated tumours and to protection against tumour rechallenge. Membrane-inserting ligands for specific CARs may facilitate the development of adoptive cell therapies that work independently of antigen expression and of tissue of origin.
Insights
Chimaeric antigen receptor (CAR) T cell therapy for solid tumors can be improved by
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Chimaeric antigen receptor (CAR) T cell therapy faces challenges in solid tumor treatment due to heterogeneous antigen expression and off-target toxicities.
- Effective CAR T cell therapy requires precise targeting to maximize efficacy and minimize adverse effects in cancer treatment.
Purpose of the Study:
- To develop a novel strategy for CAR T cell therapy that overcomes antigen heterogeneity in solid tumors.
- To investigate the efficacy of targeting tumor cells via membrane-inserted ligands for CAR T cells.
Main Methods:
- Developed CAR T cells specific for fluorescein isothiocyanate (FITC).
- Administered FITC-conjugated lipid-poly(ethylene)-glycol amphiphiles intratumorally to tag tumor cell membranes.
- Evaluated therapeutic effects in syngeneic and human tumor xenografts in mice.
Main Results:
- Amphiphile tagging of tumor cells led to significant tumor regression.
- FITC-specific CAR T cells proliferated and accumulated within tumors, demonstrating targeted cell accumulation.
- Therapy induced endogenous T cell responses, including infiltration and priming, and provided systemic anti-tumor activity and long-term protection against tumor rechallenge.
Conclusions:
- Membrane-inserting ligands offer a promising approach for CAR T cell therapy in solid tumors, independent of tumor antigen expression.
- This strategy enhances CAR T cell efficacy by enabling tumor targeting and stimulating endogenous immune responses.
- Amphiphile tagging represents a potential breakthrough for developing broadly applicable adoptive cell therapies for various cancers.
