Engineered CAR T cells targeting mesothelin by  piggyBac  transposon system for the treatment of pancreatic cancer

He, Jiang-Chuan; Zhang, Zhiwei; Lv, Sai-Qun; Liu, Xiangzhen; Cui, Lianzhen; Jiang, Duqing; Zhang, Qi; Li, Linfang; Qin, Wenxia; Jin, Haixia; Qian, Qijun

doi:10.1016/j.cellimm.2018.04.007

Cited by 32 publications

(30 citation statements)

References 41 publications

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“…The MSLN-CAR-T could kill cancer cells with high MSLN expression in vitro. 25 In a mouse model, approximately 30 days after 10 7 CAR-T cells were injected intravenously, metabolic imaging showed that tumors in these mice almost completely disappeared, while no other visceral dysfunction was observed. Similar results were also found in the study of Hua et al 26 Currently, many clinical studies of MSLN-CAR-T therapy targeting PDAC are in progress.…”

Section: Mesothelinmentioning

confidence: 96%

“…He et al generated a second‐generation CAR‐T that targeted MSLN using the piggyBac transposon system. The MSLN‐CAR‐T could kill cancer cells with high MSLN expression in vitro . In a mouse model, approximately 30 days after 10 7 CAR‐T cells were injected intravenously, metabolic imaging showed that tumors in these mice almost completely disappeared, while no other visceral dysfunction was observed.…”

Section: Car‐t Targets In Pdacmentioning

confidence: 99%

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Research progress and design optimization of CAR‐T therapy for pancreatic ductal adenocarcinoma

et al. 2019

Cancer Medicine

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Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Chimeric antigen receptor T cells (CAR‐T) are genetically engineered T cells that can specifically kill tumor cells without major histocompatibility complex restriction. Encouraging progress in CAR‐T therapy for PDAC has been made in preclinical and early phase clinical trials. Challenges in CAR‐T therapy for solid tumors still exist, including immunosuppressive microenvironment, interstitial barrier, poor chemotaxis, and the “on‐target, off‐tumor” effect. Applying neoantigens of PDAC as targets for CAR‐T therapy, recognizing the CAR‐T subgroup with better antitumor effect, and designing a CAR‐T system targeting stroma of PDAC may contribute to develop a powerful CAR‐T therapy for PDAC in the future.

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Section: Mesothelinmentioning

confidence: 96%

Section: Car‐t Targets In Pdacmentioning

confidence: 99%

Research progress and design optimization of CAR‐T therapy for pancreatic ductal adenocarcinoma

et al. 2019

Cancer Medicine

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“…With this in mind, an article from 2017 [65] summarized the possible targets of CAR T-cells in pancreatic cancer and added CD24, prostate stem cell antigen, and natural killer receptors for the construction of CARs. By showing high expression, mesothelin appears to be the most promising target for CARs [66][67][68][69]. Other research [70] focused on blocking IL-10 with the purpose of tackling the immunosuppressive effect of the tumor microenvironment and enhancing mesothelin CAR T-cell activity.…”

Section: Pancreatic Cancermentioning

confidence: 99%

Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer

Sur

Havași

Căinap

et al. 2020

JCM

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Chimeric antigen receptor (CAR) T-cell therapy represents a new genetically engineered method of immunotherapy for cancer. The patient’s T-cells are modified to express a specific receptor that sticks to the tumor antigen. This modified cell is then reintroduced into the patient’s body to fight the resilient cancer cells. After exhibiting positive results in hematological malignancies, this therapy is being proposed for solid tumors like colorectal cancer. The clinical data of CAR T-cell therapy in colorectal cancer is rather scarce. In this review, we summarize the current state of knowledge, challenges, and future perspectives of CAR T-cell therapy in colorectal cancer. A total of 22 articles were included in this review. Eligible studies were selected and reviewed by two researchers from 49 articles found on Pubmed, Web of Science, and clinicaltrials.gov. This therapy, at the moment, provides modest benefits in solid tumors. Not taking into consideration the high manufacturing and retail prices, there are still limitations like increased toxicities, relapses, and unfavorable tumor microenvironment for CAR T-cell therapy in colorectal cancer.

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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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Engineered CAR T cells targeting mesothelin by piggyBac transposon system for the treatment of pancreatic cancer

Cited by 32 publications

References 41 publications

Research progress and design optimization of CAR‐T therapy for pancreatic ductal adenocarcinoma

Research progress and design optimization of CAR‐T therapy for pancreatic ductal adenocarcinoma

Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer

Overhauling CAR T Cells to Improve Efficacy, Safety and Cost

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