Abstract
With the exception of viral-induced malignances such as cervical cancer, high-affinity proinflammatory T cells specific for tumor-associated antigens (TAA) are either deleted or rendered anergic as a consequence of central and peripheral tolerance. Reprogramming of peripheral blood-derived T cells while preserving their full functional potential to recognize and kill tumor cells is thus required to circumvent negative selection processes. One tactic for redirecting specificity is through genetic modification of T cells to express a chimeric antigen receptor (CAR) targeting a TAA such as CD19, which is expressed on B-lineage malignancies, and their subsequent adoptive transfer into cancer patients. Transposon-based gene transfer is an alternative method to retroviral transduction for integrating such transgenes into the T-cell genome. The Sleeping Beauty (SB) transposon system is a safe and low-cost technique for engineering T cells to express a CD19-specific CAR from a plasmid. This gene-transfer approach provides sufficient transgene integration for retrieval of clinically sufficient numbers of CAR+ T cells for clinical translation into the first-in-human clinical trial already enrolling patients.
Keywords: Cancer, DNA transposons, gene therapy, T cells, transposition, Sleeping Beauty
Current Drug Therapy
Title:Transposon-Based Engineering of Clinical-Grade T Cells for Cancer Therapy
Volume: 7 Issue: 1
Author(s): Kirsten Switzer, Brian Rabinovich and Laurence J.N. Cooper
Affiliation:
Keywords: Cancer, DNA transposons, gene therapy, T cells, transposition, Sleeping Beauty
Abstract: With the exception of viral-induced malignances such as cervical cancer, high-affinity proinflammatory T cells specific for tumor-associated antigens (TAA) are either deleted or rendered anergic as a consequence of central and peripheral tolerance. Reprogramming of peripheral blood-derived T cells while preserving their full functional potential to recognize and kill tumor cells is thus required to circumvent negative selection processes. One tactic for redirecting specificity is through genetic modification of T cells to express a chimeric antigen receptor (CAR) targeting a TAA such as CD19, which is expressed on B-lineage malignancies, and their subsequent adoptive transfer into cancer patients. Transposon-based gene transfer is an alternative method to retroviral transduction for integrating such transgenes into the T-cell genome. The Sleeping Beauty (SB) transposon system is a safe and low-cost technique for engineering T cells to express a CD19-specific CAR from a plasmid. This gene-transfer approach provides sufficient transgene integration for retrieval of clinically sufficient numbers of CAR+ T cells for clinical translation into the first-in-human clinical trial already enrolling patients.
Export Options
About this article
Cite this article as:
Switzer Kirsten, Rabinovich Brian and J.N. Cooper Laurence, Transposon-Based Engineering of Clinical-Grade T Cells for Cancer Therapy, Current Drug Therapy 2012; 7 (1) . https://dx.doi.org/10.2174/157488512800389155
DOI https://dx.doi.org/10.2174/157488512800389155 |
Print ISSN 1574-8855 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3903 |
Call for Papers in Thematic Issues
Novel Therapeutic Approaches and Biomarkers for Chronic Kidney Disease (CKD)
The thematic issue on "Novel Therapeutic Approaches and Biomarkers for CKD" aims to provide a comprehensive exploration of cutting-edge strategies for the management of chronic kidney disease (CKD). This issue will delve into emerging therapeutic targets, focusing on critical aspects such as podocyte injury, endothelial dysfunction, and tubulointerstitial fibrosis, which ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Working Towards the Development of Vaccines for the Treatment and Prevention of Early Breast Cancer
Current Cancer Therapy Reviews Promising Protective Effects of Chrysin in Cardiometabolic Diseases
Current Drug Targets Role of Calcium, Vitamin D, and the Extrarenal Vitamin D Hydroxylases in Carcinogenesis
Anti-Cancer Agents in Medicinal Chemistry Apoptosis: Potential Therapeutic Targets for New Drug Discovery
Current Medicinal Chemistry Genetics of Bladder Malignant Tumors in Childhood
Current Genomics Molecular and Clinical Analysis of Predictive Biomarkers in Non-Small-Cell Lung Cancer
Current Medicinal Chemistry p42.3 in Gastric Carcinoma: A Novel Biomarker and Promising Therapeutic Target
Letters in Drug Design & Discovery Functional Properties of Kefiran in the Medical Field and Food Industry
Current Pharmaceutical Biotechnology Curcumin as an Anti-Cancer Agent: Review of the Gap Between Basic and Clinical Applications
Current Medicinal Chemistry Biology of Cox-2: An Application in Cancer Therapeutics
Current Drug Targets Recent Developments in the Chemical Biology of Epothilones
Current Pharmaceutical Design Infectious Co-Factors in HIV-1 Transmission Herpes Simplex Virus Type-2 and HIV-1: New Insights and Interventions
Current HIV Research Paraneoplastic Pemphigus: Autoimmune-Cancer Nexus in the Skin
Anti-Cancer Agents in Medicinal Chemistry Human Cancer Cell Line Based Approach of 1,3,4-thiadiazole and its Fused Ring: A Comprehensive Review
Anti-Cancer Agents in Medicinal Chemistry Co-delivery Strategies Based on Multifunctional Nanocarriers for Cancer Therapy
Current Drug Metabolism Flavonoids as Sirtuin Modulators
Current Topics in Medicinal Chemistry Peripheral TRPV1 Receptors As Targets for Drug Development: New Molecules and Mechanisms
Current Pharmaceutical Design Free Flap Head and Neck Reconstruction After Cancer Therapy: Current State of the Art
Current Cancer Therapy Reviews Molecular Targets of Tannic Acid in Alzheimer's Disease
Current Alzheimer Research Characteristics of HSV-2, <i>M. genitalium</i> and <i>C. trachomatis</i> in HPV Genotypes Associated with Cervical Intraepithelial Neoplasia and Genital Infections
Infectious Disorders - Drug Targets