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Generation and functional characterization of CAR exosomes
Chuqi Wang1, Wenyan Fu2, Changhai Lei1
1Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai, China.
Methods in Cell Biology
|February 14, 2022
Summary
Chimeric antigen receptor (CAR) T-cell therapy shows promise but has toxicities. CAR exosomes, derived from CAR T-cells, offer a safer alternative by inhibiting tumor growth without causing cytokine release syndrome.
Area of Science:
- Immunotherapy
- Oncology
- Nanomedicine
- Extracellular Vesicles
Background:
- Chimeric antigen receptor (CAR) T-cell therapy is a potent cancer treatment, but faces challenges including cytokine release syndrome and tumor immune evasion.
- Exosomes, small extracellular vesicles, are explored as drug delivery vehicles due to their natural cargo transport capabilities.
Purpose of the Study:
- To investigate CAR T-cells' ability to release CAR-expressing exosomes (CAR exosomes).
- To evaluate the therapeutic potential and safety profile of CAR exosomes compared to CAR T-cells.
Main Methods:
- CAR T-cells were stimulated with antigens to induce the release of extracellular vesicles.
- The released vesicles were characterized as CAR exosomes, with surface CAR expression and cytotoxic molecule content.
- The efficacy and safety of CAR exosomes were assessed in preclinical models, including cytokine release syndrome models.
Main Results:
- CAR T-cells release antigen-stimulated exosomes displaying CARs on their surface.
- These CAR exosomes exhibit potent, antigen-specific tumor-inhibitory activity and lack PD-1, circumventing tumor immunosuppression.
- CAR exosomes demonstrated a reduced risk of cytokine release syndrome compared to CAR T-cell therapy in vivo.
Conclusions:
- CAR exosomes represent a promising cell-free therapeutic alternative to CAR T-cell therapy.
- Their inherent safety profile and efficacy against tumors, including solid tumors, warrant further investigation for clinical application.
