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Positron Emission Tomography Imaging of Cell Trafficking: A Method of Cell Radiolabeling
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ST3GAL1 and βII-spectrin pathways control CAR T cell migration to target tumors
Yeonsun Hong1, Brandon L Walling1, Hye-Ran Kim1
1Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, USA.
Nature Immunology
|April 17, 2023
Summary
Researchers identified ST3GAL1 as a target to improve CAR T cell therapy for solid tumors. Enhancing βII-spectrin reversed ST3GAL1
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Chimeric antigen receptor (CAR) T cell therapy shows promise for hematological cancers but struggles with solid tumors.
- CAR T cell migration to tumors is crucial for effective immunotherapy.
Purpose of the Study:
- To identify novel regulators of CAR T cell migration in solid tumors.
- To explore strategies for enhancing CAR T cell homing and efficacy.
Main Methods:
- Conducted a CRISPR-Cas9 pooled loss-of-function screen in vivo.
- Analyzed glycosylated proteins and T cell migration patterns.
- Engineered CAR T cells with modified βII-spectrin expression.
Main Results:
- Identified ST3GAL1 (ST3 β-galactoside α-2,3-sialyltransferase 1) as a negative regulator of CAR T cell migration.
- ST3GAL1-mediated glycosylation of CD18 alters LFA-1 recycling, causing nonspecific T cell sequestration.
- Enhanced βII-spectrin expression in CAR T cells reversed ST3GAL1 effects, improving tumor homing and reducing tumor growth in mice.
Conclusions:
- The ST3GAL1-βII-spectrin axis is a key intrinsic regulator of CAR T cell migration.
- Targeting this axis offers a promising strategy to enhance CAR T cell immunotherapy for solid tumors.
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