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 |
- 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
-
The Role of microRNAs in the Diagnosis and Treatment of Malignant Pleural Mesothelioma - A Short Review
MicroRNA β-estradiol Induces Mitochondrial Apoptosis in Cervical Cancer through the Suppression of AKT/NF-κB Signaling Pathway
Recent Patents on Anti-Cancer Drug Discovery Combined Cancer Therapy with Non-Conventional Drugs: All Roads Lead to AMPK
Mini-Reviews in Medicinal Chemistry Obesity-Driven Inflammation and Colorectal Cancer
Current Medicinal Chemistry Fibrates in the Chemical Action of Daunorubicin
Current Cancer Drug Targets Oncolytic Virus: Regulatory Aspects from Quality Control to Clinical Studies
Current Cancer Drug Targets Human Papillomavirus E7 Oncoprotein Promotes Proliferation and Migration through the Transcription Factor E2F1 in Cervical Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Gene Directed Enzyme Prodrug Therapy for Ovarian Cancer: Could GDEPT Become a Promising Treatment Against Ovarian Cancer?
Anti-Cancer Agents in Medicinal Chemistry Regulating miRNA by Natural Agents as a New Strategy for Cancer Treatment
Current Drug Targets Editorial [Hot Topic: The RB-Pathway in Cancer (Executive Editor: Erik Knudsen)]
Current Molecular Medicine The Effectiveness of Condoms for the Prevention of Sexually Transmitted Diseases
Current Women`s Health Reviews Theranostic Radiopharmaceuticals Targeting Cancer-Associated Fibroblasts
Current Radiopharmaceuticals Novel VEGF-independent Strategies Targeting Tumor Vasculature: Clinical Aspects
Current Pharmaceutical Design Platinum Compounds: A Hope for Future Cancer Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry The Macrophage Stimulating Protein/Ron Pathway as a Potential Therapeutic Target to Impede Multiple Mechanisms Involved in Breast Cancer Progression
Current Drug Targets Recent Innovations in Antibody-Mediated, Targeted Particulate Nanotechnology and Implications for Advanced Visualisation and Drug Delivery
Current Nanoscience BUB1B Promotes Proliferation of Prostate Cancer via Transcriptional Regulation of MELK
Anti-Cancer Agents in Medicinal Chemistry Diffuse Large B-Cell Lymphoma Presenting as an Anterior Chest Wall Mass: A Case Report and Literature Review
Current Respiratory Medicine Reviews Ovarian Cancer - Angiogenesis and Targeted Therapy
Current Angiogenesis (Discontinued) Phytochemical Characterization of Prickly Pear (Opuntia spp.) and of its Nutritional and Functional Properties: A Review
Current Nutrition & Food Science