Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice

Li, He; Huang, Yao Qi; Jiang, Duqing; Cui, Lianzhen; He, Zhiwei; Wang, Chao; Zhang, Zhiwei; Zhu, Haili; Ding, Yongmei; Li, Linfang; Li, Qiang; Jin, Haixia; Qian, Qijun

doi:10.1038/s41419-017-0238-6

Cited by 79 publications

(54 citation statements)

References 41 publications

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“… 24 As EGFR is highly expressed in head and neck squamous cell carcinoma, it can theoretically be used as a target in the construction of CART cells. 25 CART cell therapy targeted to EGFR has been studied in cancers such as non-small-cell lung cancer and malignant gliomas. To date, no research has been done on head and neck squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

The functional verification of EGFR-CAR T-cells targeted to hypopharyngeal squamous cell carcinoma

Dong¹,

Ding²,

Wei³

et al. 2018

OTT

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BackgroundThe aim of this study was to validate the antitumor function of EGFR-chimeric antigen T-cells (CART) targeted to FaDu cells, a hypopharyngeal squamous cell carcinoma cell line, and to provide a preclinical basis for the application of CART cell technology in hypopharyngeal squamous cell carcinoma.MethodsDetection of cytokine secretions of EGFR-CAR T and CART-controls in the presence of target cells and nontarget cells as an indicator of CART cell activation. Detection of the cytotoxic effects of EGFR-CAR T on specific tumors in the presence of target cells was evaluated by LDH release and CART cell proliferation.ResultsThe results showed that cytokine secretion increased significantly after EGFR-CAR T-cells were incubated with target cells, and EGFR-CAR T-cells has higher cytotoxic effect on target cells than the CART-control group. The target cell lysis rate was 52.66%. The proliferation of EGFR-CAR T-cells in the presence of target cells was not distinctly observed.ConclusionIn this study, we validated the antitumor function of EGFR-CAR T-cells targeted to the FaDu cell line and provided the foundation for application of the CART technique in the treatment of hypopharyngeal carcinoma.

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Section: Discussionmentioning

confidence: 99%

The functional verification of EGFR-CAR T-cells targeted to hypopharyngeal squamous cell carcinoma

Dong¹,

Ding²,

Wei³

et al. 2018

OTT

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“…Another limitation is the need of large-scale production of viral vectors and associated quality control performed by highly competent technicians [28,128]. To surpass these bottlenecks, non-viral technologies, including Sleeping Beauty and PiggyBac transposon-based vectors [129,130], pDNA transfection [131,132], or different nanoformulations (reviewed in [35]), are being pursued.…”

Section: Car-t Cells Therapymentioning

confidence: 99%

Gene Therapy in Cancer Treatment: Why Go Nano?

et al. 2020

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The proposal of gene therapy to tackle cancer development has been instrumental for the development of novel approaches and strategies to fight this disease, but the efficacy of the proposed strategies has still fallen short of delivering the full potential of gene therapy in the clinic. Despite the plethora of gene modulation approaches, e.g., gene silencing, antisense therapy, RNA interference, gene and genome editing, finding a way to efficiently deliver these effectors to the desired cell and tissue has been a challenge. Nanomedicine has put forward several innovative platforms to overcome this obstacle. Most of these platforms rely on the application of nanoscale structures, with particular focus on nanoparticles. Herein, we review the current trends on the use of nanoparticles designed for cancer gene therapy, including inorganic, organic, or biological (e.g., exosomes) variants, in clinical development and their progress towards clinical applications.

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“…The PiggyBac, Sleeping Beauty and Tol2 transposons are all being explored for the transfer of CAR constructs, with CD19 being the typical target antigen [ 125 , 127 , 128 ]. Even so, transposon mediated gene transfer of CARs targeting mesothelin [ 129 ], CD56 [ 130 ], EGFR (epidermal growth factor receptor) [ 131 ], CD116 [ 132 ], IGF1R (insulin-like growth factor 1 receptor) and ROR1 (receptor tyrosine kinase like orphan receptor 1) [ 133 ] and HERV-K (human endogenous retrovirus-K) [ 134 ] have been reported. So far, clinical data is available from parallel Phase I trials where Sleeping Beauty was used to transfer a CD19 CAR to T cells which were used for the treatment of a total of 26 patients with advanced non-Hodgkin lymphoma or acute lymphoblastic leukemia.…”

Section: New Routes For Gene Transfer: Bringing the Car To The Celmentioning

confidence: 99%

Overhauling CAR T Cells to Improve Efficacy, Safety and Cost

Chicaybam

Bonamino

Invitti

et al. 2020

Cancers

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Gene therapy is now surpassing 30 years of clinical experience and in that time a variety of approaches has been applied for the treatment of a wide range of pathologies. While the promise of gene therapy was over-stated in the 1990’s, the following decades were met with polar extremes between demonstrable success and devastating setbacks. Currently, the field of gene therapy is enjoying the rewards of overcoming the hurdles that come with turning new ideas into safe and reliable treatments, including for cancer. Among these modalities, the modification of T cells with chimeric antigen receptors (CAR-T cells) has met with clear success and holds great promise for the future treatment of cancer. We detail a series of considerations for the improvement of the CAR-T cell approach, including the design of the CAR, routes of gene transfer, introduction of CARs in natural killer and other cell types, combining the CAR approach with checkpoint blockade or oncolytic viruses, improving pre-clinical models as well as means for reducing cost and, thus, making this technology more widely available. While CAR-T cells serve as a prime example of translating novel ideas into effective treatments, certainly the lessons learned will serve to accelerate the current and future development of gene therapy drugs.

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Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice

Cited by 79 publications

References 41 publications

The functional verification of EGFR-CAR T-cells targeted to hypopharyngeal squamous cell carcinoma

The functional verification of EGFR-CAR T-cells targeted to hypopharyngeal squamous cell carcinoma

Gene Therapy in Cancer Treatment: Why Go Nano?

Overhauling CAR T Cells to Improve Efficacy, Safety and Cost

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