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Functional expression of chimeric receptor genes in human T cells
1Department of Immunology, The Weizmann Institute of Science, 76100, Rehovot, Israel. zelig.eshhar@weizmann.ac.il
Journal of Immunological Methods
|February 27, 2001
Summary
Researchers optimized T cell transfection for cancer immunotherapy. This novel T body system redirects lymphocytes to target tumors, enhancing therapeutic potential for cancer patients.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Cancer immunotherapy faces challenges like poor tumor antigenicity and patient immunocompromise.
- Current antibody therapies have limitations in tumor penetration and half-life.
Purpose of the Study:
- To optimize conditions for efficient retroviral transduction of human peripheral lymphocytes (PBL) for cancer immunotherapy.
- To develop a T body system for redirecting effector lymphocytes against tumor targets.
Main Methods:
- Utilized retroviral vectors pseudotyped with gibbon ape leukemia virus (GaLV) envelope for PBL transduction.
- Employed a tripartite chimeric receptor construct including antibody V region, CD28, and gamma activation molecule.
- Optimized transduction by co-activating PBL with anti-CD3 and anti-CD28 antibodies and using green fluorescent protein (GFP) for selection.
Main Results:
- Achieved stable and efficient transduction of human PBL, with transgene expression in 35-70% of T cells.
- Transduced lymphocytes expressed chimeric receptors, produced IL-2 upon stimulation, and proliferated without exogenous IL-2.
- Demonstrated effective lysis of target cells expressing the TNP hapten by transduced lymphocytes.
Conclusions:
- Established optimal conditions for transfecting effector lymphocytes to redirect them against tumor targets.
- The T body system shows promise for enhancing cancer immunotherapy efficacy.
- This approach offers a potential strategy to overcome limitations of current immunotherapies.