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PiggyBac-engineered T cells expressing a glypican-3-specific chimeric antigen receptor show potent activities against hepatocellular carcinoma
- Source :
- Immunobiology. 225:151850
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Glypican-3 (GPC3) is an attractive target for chimeric antigen receptor (CAR)-T cell therapy, as it is overexpressed in most hepatocellular carcinoma (HCC) tissues but shows restricted expression in healthy adult tissues. Herein, we generated GPC3-specific CAR-T cells for HCC therapy by electroporation with plasmid DNA encoding the piggyBac (PB) transposon and the hyperactive piggyBac transposase simultaneously instead of by commonly-used viral vectors. Our results demonstrated that GPC3CAR gene was efficiently integrated into the genome of T cells utilizing the PB transposon system. Upon stimulation with GPC3 antigen, GPC3CAR-T cells could be effectively activated, proliferate strongly and secrete high levels of cytokines. It also was demonstrated that GPC3CAR-T cells displayed potent cytotoxicity against GPC3-positive HCC cell lines in vitro by using real-time cell analyser (RTCA) system and the JuLI™ Stage Cell History Recorder. More importantly, in a Huh-7 xenograft mouse model, GPC3CAR-T cells significantly reduced the tumour burden companied with the secretion of high levels of IFN-γ. Moreover, T cells in mice treated with GPC3CAR-T cells could infiltrate into tumour tissues and persist as effector memory T cells (TEM). Overall, our study suggests that the use of PB system-based GPC3CAR-T cell therapy could be a promising clinical strategy for patients with HCC.
- Subjects :
- Cytotoxicity, Immunologic
0301 basic medicine
Carcinoma, Hepatocellular
T-Lymphocytes
Immunology
Cell
Receptors, Antigen, T-Cell
Nerve Tissue Proteins
T-Cell Antigen Receptor Specificity
Mice, SCID
Lymphocyte Activation
Immunotherapy, Adoptive
Glypican 3
Viral vector
Cell therapy
Mice
03 medical and health sciences
0302 clinical medicine
Glypicans
Antigen
Cell Line, Tumor
medicine
Animals
Humans
Immunology and Allergy
Transgenes
Cell Proliferation
Chemistry
Electroporation
Liver Neoplasms
Hematology
Xenograft Model Antitumor Assays
Chimeric antigen receptor
030104 developmental biology
medicine.anatomical_structure
Cell culture
Cancer research
Female
Genetic Engineering
030215 immunology
Subjects
Details
- ISSN :
- 01712985
- Volume :
- 225
- Database :
- OpenAIRE
- Journal :
- Immunobiology
- Accession number :
- edsair.doi.dedup.....24d63324445718a44c73d0052aae28c3