Intraperitoneal immunotherapy with T cells stably and transiently expressing anti-EpCAM CAR in xenograft models of peritoneal carcinomatosis

Ang, Wei Xia; Li, Zhendong; Chi, Zhixia; Du, Shouhui; Chen, Can; Tay, Johan Chin-Kang; Toh, Han Chong; Connolly, John E.; Xu, Xue Hu; Wang, Shu

doi:10.18632/oncotarget.14592

Cited by 92 publications

(80 citation statements)

References 40 publications

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“…Daly et al developed CAR-T cells with a chimeric receptor recognizing the colorectal cancer-associated antigen EGP40 [ 9 ]. Ang et al developed EpCAM-specific CAR-T cells and used the CAR-T cells to treat mice with colorectal cancer xenografts [ 10 ]. In addition to these preclinical studies, four groups carried out clinical trials in which CRC was treated with CAR-T cells targeting HER2 [ 11 ], TAG-72 [ 12 ], CEA [ 13 ], or CEACAM5 [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models

Zhang

Ding

et al. 2018

Journal of Immunology Research

113

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Adoptive chimeric antigen receptor-modified T or NK cells (CAR-T or CAR-NK) offer new options for cancer treatment. CAR-T therapy has achieved encouraging breakthroughs in the treatment of hematological malignancies. However, their therapeutic efficacy against solid tumors is limited. New regimens, including combinations with chemical drugs, need to be studied to enhance the therapeutic efficacy of CAR-T or NK cells for solid tumors. An epithelial cell adhesion molecule- (EpCAM-) specific second-generation CAR was constructed and transduced into NK-92 cells by lentiviral vectors. Immune effects, including cytokine release and cytotoxicity of the CAR-NK-92 cells against EpCAM-positive colon cancer cells, were evaluated in vitro. Synergistic effects of regorafenib and CAR-NK-92 cells were analyzed in a mouse model with human colorectal cancer xenografts. The CAR-NK-92 cells can specifically recognize EpCAM-positive colorectal cancer cells and release cytokines, including IFN-γ, perforin, and granzyme B, and show specific cytotoxicity in vitro. The growth suppression efficacy of combination therapy with regorafenib and CAR-NK-92 cells on established EpCAM-positive tumor xenografts was more significant than that of monotherapy with CAR-NK-92 cells or regorafenib. Our results provided a novel strategy to treat colorectal cancer and enhance the therapeutic efficacy of CAR-modified immune effector cells for solid tumors.

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Section: Introductionmentioning

confidence: 99%

Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models

Zhang

Ding

et al. 2018

Journal of Immunology Research

113

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“…Regional delivery of CAR T-cell compared to systemic infusions resulted in enhanced anti-tumor effects for peritoneal carcinomatosis [116]. For peritoneal carcinomatosis, an EpCAMtargeting CAR T-cell construct exhibited anti-tumor efficacy for mouse models of human ovarian cancer and CRC [117]. EpCAM proved to be a suitable target for CARs in a xenograft mouse model.…”

Section: Car T-cell Therapy Studies For Crcmentioning

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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“…is considered local delivery, again emphasizing one of the major considerations when mRNA CAR T cell is used to eradicate solid tumor. Additional novel target explorations for mRNA CAR T cell therapy have included melanoma-associated chondroitin sulfate proteoglycan (MCSP), CEA, and vascular endothelial growth factor receptor 2 (VEGFR2) for melanoma; [40][41][42] epithelial cell adhesion molecule (EpCAM) for gastric and ovarian cancer; 43 epidermal growth factor receptor (EGFR) for glioblastoma; 44 and Natural Killer group 2D ligand (NKGD2L) for Ewing's sarcoma. 45 Tchou et al 46 recently targeted c-Met, a cell-surface protein present in a variety of solid tumors.…”

Section: Car-encoding Ivt Mrna Directed To Other Targets On Solid Tumorsmentioning

confidence: 99%

The Emerging Role of In Vitro-Transcribed mRNA in Adoptive T Cell Immunotherapy

2019

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Adoptive T cell therapy is a form of cellular therapy that utilizes human immune cells, often empowered by the expression of recombinant proteins, to attack selected targets present on tumor or infected cells. T cell-based immunotherapy has been progressing over the past several decades, and reached a milestone with the recent US Food and Drug Administration (FDA) approval of chimeric antigen receptor T cell therapy for relapsed and refractory leukemia and lymphoma. Although most studies have used viral vectors, a growing number of researchers have come to appreciate in vitro-transcribed (IVT) mRNA for the development, testing, and application of T cell-based immunotherapeutics. IVT mRNA offers inherent safety features, highly efficient recombinant protein translation, and the ability to control pharmacokinetic properties of the therapy. In this review, we discuss the history of IVT mRNA in adoptive T cell therapy, from tumor-infiltrating lymphocytes and T cell receptor-based therapies to chimeric antigen receptor therapy and gene-editing techniques, as well as prior and ongoing clinical trials. In 2006, Rabinovich et al. 11 were the first to transduce T cells with IVT mRNA encoding chimeric antigen receptors (CARs) directed against CD19 and demonstrated functionality of those T cells in vitro. By 2009, several studies reported using IVT mRNA to create

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Intraperitoneal immunotherapy with T cells stably and transiently expressing anti-EpCAM CAR in xenograft models of peritoneal carcinomatosis

Cited by 92 publications

References 40 publications

Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models

Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models

Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer

The Emerging Role of In Vitro-Transcribed mRNA in Adoptive T Cell Immunotherapy

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