Natural killer cell–based immunotherapy: From transplantation toward targeting cancer stem cells

Dianat‐Moghadam, Hassan; Rokni, Mohsen; Marofi, Faroogh; Panahi, Yunes; Yousefi, Mehdi

doi:10.1002/jcp.26878

Cited by 55 publications

(33 citation statements)

References 120 publications

(236 reference statements)

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“…Features such as ease of accessibility and separation, high in vitro proliferation capacity, and the ability of differentiation into nonmesodermal lineage lead to its widespread use in regenerative medicine. Tissue repair, secretion of soluble factors resulting in the beneficial therapeutic effect by creating an immunomodulatory environment, selective migration to the tumor site, nonimmunogenic and high ability of genetic modification safely for production of the antitumor agent have become MSCs the best option for targeted gene therapy of cancers (Dianat‐Moghadam, Rokni, Marofi, Panahi, & Yousefi, ; Klinker & Wei, ). MSCs properties and applications are summarized and illustrated in Table and Figure .…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells as carrier of the therapeutic agent in the gene therapy of blood disorders

Shomali

Gharibi

Vahedi

et al. 2019

Journal Cellular Physiology

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Nonhematopoietic stem cells as a delivery platform of therapeutic useful genes have attracted widespread attention in recent years, owing to gained a long lifespan, easy separation, high proliferation, and high transfection capacity. Mesenchymal stem/ stromal cells (MSCs) are the choice of the cells for gene and cell therapy due to high self-renewal capacity, high migration rate to the site of the tumor, and with immune suppressive and anti-inflammatory properties. Hence, it has a high potential of safety genetic modification of MSCs for antitumor gene expression and has paved the way for the clinical application of these cells to target the therapy of cancers and other diseases. The aim of gene therapy is targeted treatment of cancers and diseases through recovery, change, or enhancement cell performance to the sustained secretion of useful therapeutic proteins and induction expression of the functional gene in intended tissue. Recent developments in the vectors designing leading to the increase and durability of expression and improvement of the safety of the vectors that overcome a lot of problems, such as durability of expression and the host immune response. Nowadays, gene therapy approach is used by MSCs as a delivery vehicle in the preclinical and the clinical trials for the secretion of erythropoietin, recombinant antibodies, coagulation factors, cytokines, as well as angiogenic inhibitors in many blood disorders like anemia, hemophilia, and malignancies. In this study, we critically discuss the status of gene therapy by MSCs as a delivery vehicle for the treatment of blood disorders. Finally, the results of clinical trial studies are assessed, highlighting promising advantages of this emerging technology in the clinical setting.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells as carrier of the therapeutic agent in the gene therapy of blood disorders

Shomali

Gharibi

Vahedi

et al. 2019

Journal Cellular Physiology

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“…Since the first characterization of NK cells, immune cells have been continuously developed for clinical applications in cancer immunotherapy in autologous or allogeneic settings, and there are now an estimated 400 NK cell‐based immunotherapy clinical trials for various types of cancer being conducted worldwide 22 . Despite the numerous ongoing clinical studies involving NK cells and the vast repertoire of historical research reports, infused NK cells have shown short persistency, limited proliferation and inaccurate tumor‐targeting in patients, resulting in poor therapeutic efficacy 23‐27 .…”

Section: Discussionmentioning

confidence: 99%

Non–clinical efficacy, safety and stable clinical cell processing of induced pluripotent stem cell‐derived anti–glypican‐3 chimeric antigen receptor‐expressing natural killer/innate lymphoid cells

et al. 2020

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The use of allogeneic, pluripotent stem-cell-derived immune cells for cancer immunotherapy has been the subject of recent clinical trials. In Japan, investigator-initiated clinical trials will soon begin for ovarian cancer treatment using human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cell (iPSC)-derived antiglypican-3 (GPC3) chimeric antigen receptor (CAR)-expressing natural killer/innate lymphoid cells (NK/ILC). Using pluripotent stem cells as the source for allogeneic immune cells facilitates stringent quality control of the final product, in terms of efficacy, safety and producibility. In this paper, we describe our methods for the stable, feeder-free production of CAR-expressing NK/ILC cells from CAR-transduced iPSC with clinically relevant scale and materials. The average number of cells that could be differentiated from 1.8-3.6 × 10 6 iPSC within 7 weeks was 1.8-4.0 × 10 9 . These cells showed stable CD45/CD7/CAR expression, effector functions of cytotoxicity and interferon gamma (IFN-γ) production against GPC3-expressing tumor cells. When the CAR-NK/ILC cells were injected into a GPC3-positive, ovarian-tumor-bearing, immunodeficient mouse model, we observed a significant therapeutic effect that prolonged the survival of the animals. When the cells were injected into immunodeficient mice during non-clinical safety tests, no acute systemic toxicity or tumorigenicity of the final product or residual iPSC was observed. In addition, our test results for the CAR-NK/ILC cells generated with clinical manufacturing standards are encouraging, and these methods should accelerate the development of allogeneic pluripotent stem cell-based immune cell cancer therapies. K E Y W O R D Schimeric antigen receptor, GPC3, ILC, immunotherapy, iPSC, NK | 1479 UEDA Et Al.

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“…Conventional mAbs may interact with CD16 on NK cells thus enhancing their capability to eliminate CSCs by boosting ADCC. Also, bispecific antibodies are under development in order to improve the physical interaction between NK cells and CSCs …”

Section: Natural Killer Cells and Solid Tumor Derived Cancer Stem Cellsmentioning

confidence: 99%

“…Also, bispecific antibodies are under development in order to improve the physical interaction between NK cells and CSCs. 128…”

Section: And Solid Tumor Derived Cancer Stem Cellsmentioning

confidence: 99%

New avenues for melanoma immunotherapy: Natural Killer cells?

et al. 2020

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Human solid malignant tumours may be particularly resistant to conventional therapies. Among solid tumours, immunological features of cutaneous melanoma have been well characterized in the past and today melanoma patients are routinely treated with the anti‐immune checkpoints immunotherapy that has completely changed metastatic melanoma treatment and prognosis. Two cytotoxic cell populations may lead to the physical elimination of tumour cell targets: cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Tumour recognition by CTLs depends on major histocompatibility complex (MHC) class I molecules, while NK cells recognize tumours expressing low or null levels of MHC class I molecules. Despite this well‐established complementarity, NK cells are still left behind in the optimization of innovative immunotherapy approaches. NK cells are members of innate lymphoid cells (ILCs) that play a critical role in early host defence against invading pathogens and transformed cells. Recent findings suggest that NK cell frequencies directly correlate with the overall survival of ipilimumab‐treated melanoma patients. Furthermore, in vitro and in vivo evidences indicate that NK cells can selectively kill cancer stem cells, reducing tumour size and delaying metastatic progression. The aim of this review is to provide a survey of the evidences indicating NK cells as an excellent candidate to complement the newest solid tumour immunotherapy approaches.

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Natural killer cell–based immunotherapy: From transplantation toward targeting cancer stem cells

Cited by 55 publications

References 120 publications

Mesenchymal stem cells as carrier of the therapeutic agent in the gene therapy of blood disorders

Mesenchymal stem cells as carrier of the therapeutic agent in the gene therapy of blood disorders

Non–clinical efficacy, safety and stable clinical cell processing of induced pluripotent stem cell‐derived anti–glypican‐3 chimeric antigen receptor‐expressing natural killer/innate lymphoid cells

New avenues for melanoma immunotherapy: Natural Killer cells?

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