CRISPR knock out CTLA-4 enhances the anti-tumor activity of cytotoxic T lymphocytes

Shi, Long; Meng, Tongyu; Zhao, Zhihui; Han, Jinsheng; Zhang, Wei; Gao, Fei; Cai, Jianhui

doi:10.1016/j.gene.2017.09.010

Cited by 58 publications

(37 citation statements)

References 41 publications

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“…Su and colleagues demonstrated that gene knockout of PD1 by electroporation of plasmids encoding sgRNA and Cas9 results in significant reduction of PD1 expression, up-regulation of cytokine production, and enhanced cytotoxicity [ 111 ]. Shi and colleagues demonstrated that CTLs with knocked-out CTLA4 by CRISPR/Cas9 system significantly repress tumor growth and improve tumor eradication [ 112 ]. Therefore, a two-in-one approach including CAR-T cells and checkpoint blockade (PD1 or CTLA4) is potentially useful to improve the efficacy of T cells.…”

Section: Approaches To Improve the Car-t Cell Efficacymentioning

confidence: 99%

Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors

Zhang

2018

Mol Cancer

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The potential for adoptive cell immunotherapy as a treatment against cancers has been demonstrated by the remarkable response in some patients with hematological malignancies using autologous T cells endowed with chimeric antigen receptors (CARs) specific for CD19. Clinical efficacy of CAR-T cell therapy for the treatment of solid tumors, however, is rare due to physical and biochemical factors. This review focuses on different aspects of multiple mechanisms of immunosuppression in solid tumors. We characterize the current state of CAR-modified T cell therapy and summarize the various strategies to combat the immunosuppressive microenvironment of solid tumors, with the aim of promoting T cell cytotoxicity and enhancing tumor cell eradication.

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Section: Approaches To Improve the Car-t Cell Efficacymentioning

confidence: 99%

Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors

Zhang

2018

Mol Cancer

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“…The patients received modified cells after chemotherapy and the CRISPR-edited cells proliferated in all of the patients while no serious treatment-related adverse events were noted. This proof-of-principle study shows that CRISPRbased treatments for cancer are both safe and feasible and will serve as the basis for phase two studies, which will likely begin in the near future [69][70][71][72]. It is not yet known how these malignancies evade immune surveillance or how removal of these genes affected the efficacy of T-cells against cancer.…”

Section: Cancermentioning

confidence: 92%

Harnessing the potential of CRISPR-based platforms to advance the field of hospital medicine

McCarthy

2020

Expert Review of Anti-infective Therapy

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“…On the one hand, cytotoxic T lymphocyte-associated protein 4 (CTLA-4 or CD152) is a protein receptor expressed in activated T cells and regulatory T cells that bind to B7 ligands in antigen-presenting cells to transmit inhibitory signals to T cells following activation, downregulating IL-2 and reducing cell division. CTLA4 disruption with CRISPR/Cas9 increases TNF-α and IFN-γ secretion, leading to a significant increase in the apoptosis of human adenocarcinoma and bladder carcinoma tumor cells (106,107). On the other hand, LAG-3, a major inhibitory receptor belonging to the IgG family, has 20% similarity with CD4 and binds to MHC class II receptors with higher affinities than CD4.…”

Section: Persistence Of Car T Cellsmentioning

confidence: 99%

Using Gene Editing Approaches to Fine-Tune the Immune System

et al. 2020

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Genome editing technologies not only provide unprecedented opportunities to study basic cellular system functionality but also improve the outcomes of several clinical applications. In this review, we analyze various gene editing techniques used to finetune immune systems from a basic research and clinical perspective. We discuss recent advances in the development of programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-associated nucleases. We also discuss the use of programmable nucleases and their derivative reagents such as base editing tools to engineer immune cells via gene disruption, insertion, and rewriting of T cells and other immune components, such natural killers (NKs) and hematopoietic stem and progenitor cells (HSPCs). In addition, with regard to chimeric antigen receptors (CARs), we describe how different gene editing tools enable healthy donor cells to be used in CAR T therapy instead of autologous cells without risking graft-versus-host disease or rejection, leading to reduced adoptive cell therapy costs and instant treatment availability for patients. We pay particular attention to the delivery of therapeutic transgenes, such as CARs, to endogenous loci which prevents collateral damage and increases therapeutic effectiveness. Finally, we review creative innovations, including immune system repurposing, that facilitate safe and efficient genome surgery within the framework of clinical cancer immunotherapies.

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CRISPR knock out CTLA-4 enhances the anti-tumor activity of cytotoxic T lymphocytes

Cited by 58 publications

References 41 publications

Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors

Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors

Harnessing the potential of CRISPR-based platforms to advance the field of hospital medicine

Using Gene Editing Approaches to Fine-Tune the Immune System

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