Chimeric antigen receptor (CAR)-modified NK cells against cancer: Opportunities and challenges

Wang, Luyao; Dou, Mei; Ma, Qingxia; Yao, Ruixue; Liu, Jia

doi:10.1016/j.intimp.2019.105695

Cited by 40 publications

(35 citation statements)

References 64 publications

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“…NK cell–based anticancer therapy has achieved clinical benefits for various cancer types, especially hematologic malignancies. CAR-NK cell therapy still faces critical challenges, including difficulty in genetic manipulation of primary NK cells and difficulty in storage of CAR-NK cells ( Wang et al, 2019b ). Currently, more cell resources, such as human NK cell lines, human embryonic stem cells, induced pluripotent stem cells, and bone marrow or umbilical-cord blood, are being tested as alternative sources of therapeutic NK cells ( Wang et al, 2019a ).…”

Section: Nk Cellsmentioning

confidence: 99%

Next-Generation Immunotherapies to Improve Anticancer Immunity

Shi

Tomczak

et al. 2021

Front. Pharmacol.

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Checkpoint inhibitors are widely used immunotherapies for advanced cancer. Nonetheless, checkpoint inhibitors have a relatively low response rate, work in a limited range of cancers, and have some unignorable side effects. Checkpoint inhibitors aim to reinvigorate exhausted or suppressed T cells in the tumor microenvironment (TME). However, the TME contains various other immune cell subsets that interact to determine the fate of cytotoxic T cells. Activation of cytotoxic T cells is initiated by antigen cross-presentation of dendritic cells. Dendritic cells could also release chemokines and cytokines to recruit and foster T cells. B cells, another type of antigen-presenting cell, also foster T cells and can produce tumor-specific antibodies. Neutrophils, a granulocyte cell subset in the TME, impede the proliferation and activation of T cells. The TME also consists of cytotoxic innate natural killer cells, which kill tumor cells efficiently. Natural killer cells can eradicate major histocompatibility complex I-negative tumor cells, which escape cytotoxic T cell–mediated destruction. A thorough understanding of the immune mechanism of the TME, as reviewed here, will lead to further development of more powerful therapeutic strategies. We have also reviewed the clinical outcomes of patients treated with drugs targeting these immune cells to identify strategies for improvement and possible immunotherapy combinations.

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Section: Nk Cellsmentioning

confidence: 99%

Next-Generation Immunotherapies to Improve Anticancer Immunity

Shi

Tomczak

et al. 2021

Front. Pharmacol.

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“…Their limited time in vivo however, also raises concern about their potential efficacy. Other concerns relating to the use of CAR‐NK cells in cancer therapy include uncertainty about their ability to migrate to tumor sites, their sensitivity to cryopreservation, low transfection efficiency, and the challenge of acquiring large numbers in vitro 108 . Some of these challenges can be addressed using NK cell lines for genetic modification.…”

Section: Genetic Modification Of Killer Cells For Adoptive Cell Therapymentioning

confidence: 99%

Killers at the crossroads: The use of innate immune cells in adoptive cellular therapy of cancer

Sabry

Lowdell

2020

Stem Cells Translational Medicine

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Adoptive cell therapy (ACT) is an approach to cancer treatment that involves the use of antitumor immune cells to target residual disease in patients after completion of chemo/radiotherapy. ACT has several advantages compared with other approaches in cancer immunotherapy, including the ability to specifically expand effector cells in vitro before selection for adoptive transfer, as well as the opportunity for host manipulation in order to enhance the ability of transferred cells to recognize and kill established tumors. One of the main challenges to the success of ACT in cancer clinical trials is the identification and generation of antitumor effector cells with high avidity for tumor recognition. Natural killer (NK) cells, cytokine‐induced killers and natural killer T cells are key innate or innate‐like effector cells in cancer immunosurveillance that act at the interface between innate and adaptive immunity, to have a greater influence over immune responses to cancer. In this review, we discuss recent studies that highlight their potential in cancer therapy and summarize clinical trials using these effector immune cells in adoptive cellular therapy for the treatment of cancer.

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“…It should be also mentioned that the most current cancer immunotherapies include the application of genetically modified NK (CAR-NK) cells carrying chimeric antigen receptors that specifically target tumor cells [150,151,152]. These CAR-NK cells are presently tested in various preclinical and clinical studies and it is tempting to speculate that they might also serve as an effective tool in immunotherapy of endometriosis.…”

Section: Conclusion and Prospects For Immunotherapymentioning

confidence: 99%

NK Cells as Potential Targets for Immunotherapy in Endometriosis

Ścieżyńska

Komorowski

Soszyńska

et al. 2019

JCM

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Endometriosis is a common gynecological disease defined by the presence of endometrial-like tissue outside the uterus, most frequently on the pelvic viscera and ovaries, which is associated with pelvic pains and infertility. It is an inflammatory disorder with some features of autoimmunity. It is accepted that ectopic endometriotic tissue originates from endometrial cells exfoliated during menstruation and disseminating into the peritoneum by retrograde menstrual blood flow. It is assumed that the survival of endometriotic cells in the peritoneal cavity may be partially due to their abrogated elimination by natural killer (NK) cells. The decrease of NK cell cytotoxic activity in endometriosis is associated with an increased expression of some inhibitory NK cell receptors. It may be also related to the expression of human leukocyte antigen G (HLA-G), a ligand for inhibitory leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) receptors. The downregulated cytotoxic activity of NK cells may be due to inhibitory cytokines present in the peritoneal milieu of patients with endometriosis. The role of NK cell receptors and their ligands in endometriosis is also confirmed by genetic association studies. Thus, endometriosis may be a subject of immunotherapy by blocking NK cell negative control checkpoints including inhibitory NK cell receptors. Immunotherapies with genetically modified NK cells also cannot be excluded.

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Chimeric antigen receptor (CAR)-modified NK cells against cancer: Opportunities and challenges

Cited by 40 publications

References 64 publications

Next-Generation Immunotherapies to Improve Anticancer Immunity

Next-Generation Immunotherapies to Improve Anticancer Immunity

Killers at the crossroads: The use of innate immune cells in adoptive cellular therapy of cancer

NK Cells as Potential Targets for Immunotherapy in Endometriosis

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