Pharmacologically upregulated carcinoembryonic antigen-expression enhances the cytolytic activity of genetically-modified chimeric antigen receptor NK-92MI against colorectal cancer cells

Shiozawa, Masayuki; Chang, Chuan-Hsin; Huang, Yuan-Li; Chen, Yi-Ching; Chi, Mau-Shin; Hao, Hsu-Chao; Chang, Yue‐Cune; Takeda, Satoru; Chi, Kwan‐Hwa; Wang, Yushan

doi:10.1186/s12865-018-0262-z

Cited by 34 publications

(16 citation statements)

References 46 publications

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“…Accordingly, combination therapy with regorafenib and CAR-NK-92 cells showed superiority over monotherapy with CAR-NK-92 cells or regorafenib in terms of inhibition of CRC growth in xenografts ( 81 ). Other in vitro studies proposed that anti- carcinoembryonic antigen (CEA)-CAR NK-92MI cells selectively recognized and eliminated high CEA-expressing CRC tumor cell lines (LS174T); without any cytolytic effects on low CEA-expressing tumor cells (HCT116) ( 86 ). Interestingly, anti-CEA-CAR NK-92MI combination therapy with either histone deacetylase-inhibitor sodium butyrate (NaB) or the methylation-inhibitor 5-azacytidine (5-AZA) caused selective killing of HCT116, which imply the clinical importance of epidrugs for prompting CAR-NK cell therapeutic efficacy in human CRC ( 86 ).…”

Section: Car Nk Cells In Solid Tumorsmentioning

confidence: 99%

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

et al. 2021

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The tumor microenvironment (TME) is greatly multifaceted and immune escape is an imperative attribute of tumors fostering tumor progression and metastasis. Based on reports, the restricted achievement attained by T cell immunotherapy reflects the prominence of emerging other innovative immunotherapeutics, in particular, natural killer (NK) cells-based treatments. Human NK cells act as the foremost innate immune effector cells against tumors and are vastly heterogeneous in the TME. Currently, there exists a rapidly evolving interest in the progress of chimeric antigen receptor (CAR)-engineered NK cells for tumor immunotherapy. CAR-NK cells superiorities over CAR-T cells in terms of better safety (e.g., absence or minimal cytokine release syndrome (CRS) and graft-versus-host disease (GVHD), engaging various mechanisms for stimulating cytotoxic function, and high feasibility for ‘off-the-shelf’ manufacturing. These effector cells could be modified to target various antigens, improve proliferation and persistence in vivo, upturn infiltration into tumors, and defeat resistant TME, which in turn, result in a desired anti-tumor response. More importantly, CAR-NK cells represent antigen receptors against tumor-associated antigens (TAAs), thereby redirecting the effector NK cells and supporting tumor-related immunosurveillance. In the current review, we focus on recent progress in the therapeutic competence of CAR-NK cells in solid tumors and offer a concise summary of the present hurdles affecting therapeutic outcomes of CAR-NK cell-based tumor immunotherapies.

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Section: Car Nk Cells In Solid Tumorsmentioning

confidence: 99%

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

et al. 2021

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“…Secondly, the dose of CAR-NK cells may be difficult to apply in vivo . Previous studies have reported the optimal anti-tumour activity for CAR-NK cells in vivo , which is 1×10 7 cells/mouse (40,41). However, the titer of the lentivirus in the present study was MOI=100.…”

Section: Discussionmentioning

confidence: 99%

Development of c‑MET‑specific chimeric antigen receptor‑engineered natural killer cells with cytotoxic effects on human liver cancer HepG2 cells

Liu

Liu²,

Zhou

et al. 2019

Mol Med Report

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In recent years, cellular immunotherapy has served an important role in the combined treatment of hepatocellular carcinoma. The possibility of specific cell therapies for the treatment of solid tumours has been further explored following the success of chimeric antigen receptor (CAR)-T cell therapy in the treatment of haematological tumours. The present study aimed to evaluate the specificity and efficiency of c-MET-targeted CAR-NK cell immunotherapy on human liver cancer in vitro . A CAR structure that targeted and recognised a c-MET antigen was constructed. c-MET-CAR was transferred into primary NK cells using lentiviral infection. c-MET-positive HepG2 cells were used as an in vitro study model. The cytotoxicity assay results revealed that c-MET-CAR-NK cells exhibited more specific cytotoxicity for HepG2 cells with high c-MET expression compared with the lung cancer cell line H1299, which has low levels of c-MET expression. The results of the present study demonstrated that c-MET may be a specific and effective target for human liver cancer cell CAR-NK immunotherapy. Based on these results, CAR-NK cell-based immunotherapy may provide a potential biotherapeutic approach for liver cancer treatment in the future.

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“…This newly derived NK cell line can be efficiently transfected and displays similar characteristics to the parental NK-92 cells [155]. Most importantly, these cells kill cognate tumor cells and their cytotoxic capacity is associated with tumor antigen expression on target cells [156]. Induced expression of tumor antigen by epigenetic modifiers, such as sodium butyrate or DNA methylation inhibitor, as in the case of carcinoembryonic antigen in human colorectal cancer cells, promotes CAR NK-92MI-mediated cytotoxicity [156].…”

Section: Cancer Immunotherapymentioning

confidence: 99%

Targeting immune cells for cancer therapy

et al. 2019

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Recent years have seen a renaissance in the research linking inflammation and cancer with immune cells playing a central role in smouldering inflammation in the tumor microenvironment. Diverse immune cell types infiltrate the tumor microenvironment, and the dynamic tumor-immune cell interplay gives rise to a rich milieu of cytokines and growth factors. Fundamentally, this intricate cross-talk creates the conducive condition for tumor cell proliferation, survival and metastasis. Interestingly, the prominent impact of immune cells is expounded in their contrary pro-tumoral role, as well as their potential anti-cancer cellular weaponry. The latter is known as immunotherapy, a concept born out of evidence that tumors are susceptible to immune defence and that by manipulating the immune system, tumor growth can be successfully restrained. Naturally, a deeper understanding of the multifaceted roles of various immune cell types thus contributes toward developing innovative anti-cancer strategies. Therefore, in this review we first outline the roles played by the major immune cell types, such as macrophages, neutrophils, natural killer cells, T cells and B cells. We then explain the recently-explored strategies of immunomodulation and discuss some important approaches via an immunology perspective.

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Pharmacologically upregulated carcinoembryonic antigen-expression enhances the cytolytic activity of genetically-modified chimeric antigen receptor NK-92MI against colorectal cancer cells

Cited by 34 publications

References 46 publications

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

RETRACTED: CAR-NK Cell: A New Paradigm in Tumor Immunotherapy

Development of c‑MET‑specific chimeric antigen receptor‑engineered natural killer cells with cytotoxic effects on human liver cancer HepG2 cells

Targeting immune cells for cancer therapy

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