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Redirecting T Cell Specificity Using T Cell Receptor Messenger RNA Electroporation
Sarene Koh1, Noriko Shimasaki2, Antonio Bertoletti3
1Singapore Institute for Clinical Sciences, Brenner Center for Molecular Medicine, Agency for Science, Technology and Research, (A*STAR), 30 Medical Drive, Singapore, Singapore. sarene_koh@sics.a-star.edu.sg.
Methods in Molecular Biology (Clifton, N.J.)
|May 30, 2016
Summary
Hepatitis B virus-specific T cell receptor engineering in T lymphocytes offers a new cancer cell therapy. This method, using messenger RNA electroporation, can be scaled for therapeutic production against viral antigens in cancers like hepatocellular carcinoma.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Genetically modified T lymphocytes, expressing T cell receptors (TCRs) or chimeric antigen receptors (CARs), show promise for cancer treatment.
- Tumors expressing viral peptides are potential targets for T cell-based therapies, particularly in cancers with viral DNA integration, such as hepatocellular carcinoma (HCC) with hepatitis B virus (HBV).
Purpose of the Study:
- To describe a method for engineering hepatitis B virus (HBV)-specific T cell receptors (TCRs) in primary human T lymphocytes.
- To establish a scalable and compliant method for therapeutic T cell production.
Main Methods:
- Engineering of HBV-specific TCRs in primary human T lymphocytes via electroporation of HBV TCR messenger RNA (mRNA).
- Method designed for scalability under current good manufacturing practice (cGMP) standards.
Main Results:
- Successful engineering of HBV-specific TCRs in human T lymphocytes.
- Demonstration of a method applicable to large-scale therapeutic T cell production.
Conclusions:
- The described mRNA electroporation method provides a viable approach for generating virus-specific T cells for cancer therapy.
- This technique is adaptable for engineering T cells with TCRs targeting other viral specificities (e.g., Epstein-Barr virus, cytomegalovirus) or CARs targeting various cancer antigens.
