Chimeric Antigen Receptor-Natural Killer Cells: The Future of Cancer Immunotherapy

Habib, Shahid; Tariq, Syed Maaz; Tariq, None Moeez

doi:10.31486/toj.19.0033

Cited by 21 publications

(13 citation statements)

References 6 publications

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“…It is expected that the use of genetically modified CAR-NK cells would avoid the low persistence and low efficacy of NK cells, and the failure to migrate to the tumor site [49]. Moreover, unlike CAR-T cells, CAR-NK cells would also present spontaneous cytotoxic activity, independently of target antigen [50]. In addition, CAR-NK cells can be obtained from different sources of NK cells, such as cell lines, PB-NK, CB-NK, human embryonic stem cells (hESCs), or iPCSs [51][52][53].…”

Section: Chimeric Antigen Receptor (Car)-modified Nk Cellsmentioning

confidence: 99%

Natural Killer Cells in Immunotherapy: Are We Nearly There?

Bachiller

Battram

Perez-Amill

et al. 2020

Cancers

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Natural killer (NK) cells are potent anti-tumor and anti-microbial cells of our innate immune system. They are equipped with a vast array of receptors that recognize tumor cells and other pathogens. The innate immune activity of NK cells develops faster than the adaptive one performed by T cells, and studies suggest an important immunoregulatory role for each population against the other. The association, observed in acute myeloid leukemia patients receiving haploidentical killer-immunoglobulin-like-receptor-mismatched NK cells, with induction of complete remission was the determinant to begin an increasing number of clinical studies administering NK cells for the treatment of cancer patients. Unfortunately, even though transfused NK cells demonstrated safety, their observed efficacy was poor. In recent years, novel studies have emerged, combining NK cells with other immunotherapeutic agents, such as monoclonal antibodies, which might improve clinical efficacy. Moreover, genetically-modified NK cells aimed at arming NK cells with better efficacy and persistence have appeared as another option. Here, we review novel pre-clinical and clinical studies published in the last five years administering NK cells as a monotherapy and combined with other agents, and we also review chimeric antigen receptor-modified NK cells for the treatment of cancer patients. We then describe studies regarding the role of NK cells as anti-microbial effectors, as lessons that we could learn and apply in immunotherapy applications of NK cells; these studies highlight an important immunoregulatory role performed between T cells and NK cells that should be considered when designing immunotherapeutic strategies. Lastly, we highlight novel strategies that could be combined with NK cell immunotherapy to improve their targeting, activity, and persistence.

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Section: Chimeric Antigen Receptor (Car)-modified Nk Cellsmentioning

confidence: 99%

Natural Killer Cells in Immunotherapy: Are We Nearly There?

Bachiller

Battram

Perez-Amill

et al. 2020

Cancers

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“…With the advent of immunomodulatory agents such as checkpoint inhibition, multimodal immunotherapy can also be considered for patients (184). Lastly, the application of CAR engineering to other immune effector cells such as NK cells opens another avenue of potential innovation (185).…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

CAR T Cell Therapy for Pediatric Brain Tumors

et al. 2020

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Chimeric Antigen Receptor (CAR) T cell therapy has recently begun to be used for solid tumors such as glioblastoma multiforme. Many children with pediatric malignant brain tumors develop extensive long-term morbidity of intensive multimodal curative treatment. Others with certain diagnoses and relapsed disease continue to have limited therapies and a dismal prognosis. Novel treatments such as CAR T cells could potentially improve outcomes and ameliorate the toxicity of current treatment. In this review, we discuss the potential of using CAR therapy for pediatric brain tumors. The emerging insights on the molecular subtypes and tumor microenvironment of these tumors provide avenues to devise strategies for CAR T cell therapy. Unique characteristics of these brain tumors, such as location and associated morbid treatment induced neuro-inflammation, are novel challenges not commonly encountered in adult brain tumors. Despite these considerations, CAR T cell therapy has the potential to be integrated into treatment schema for aggressive pediatric malignant brain tumors in the future.

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“…These trials target both solid and blood malignancies. CAR-NK cells have been tested for tumor antigens (CD19, HER2, CD33, CD7, MUCI, and NR) and SARS-CoV-2 infected cells [ 179 , 180 ]. The number of clinical trials being conducted on CAR-NK cells is far lower that the number of clinical trials being conducted on CAR-T cells, which suggests that further research is required.…”

Section: Discussionmentioning

confidence: 99%

Innovative CAR-T Cell Therapy for Solid Tumor; Current Duel between CAR-T Spear and Tumor Shield

Ali

Shim

et al. 2020

Cancers

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Novel engineered T cells containing chimeric antigen receptors (CAR-T cells) that combine the benefits of antigen recognition and T cell response have been developed, and their effect in the anti-tumor immunotherapy of patients with relapsed/refractory leukemia has been dramatic. Thus, CAR-T cell immunotherapy is rapidly emerging as a new therapy. However, it has limitations that prevent consistency in therapeutic effects in solid tumors, which accounts for over 90% of all cancer patients. Here, we review the literature regarding various obstacles to CAR-T cell immunotherapy for solid tumors, including those that cause CAR-T cell dysfunction in the immunosuppressive tumor microenvironment, such as reactive oxygen species, pH, O2, immunosuppressive cells, cytokines, and metabolites, as well as those that impair cell trafficking into the tumor microenvironment. Next-generation CAR-T cell therapy is currently undergoing clinical trials to overcome these challenges. Therefore, novel approaches to address the challenges faced by CAR-T cell immunotherapy in solid tumors are also discussed here.

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Chimeric Antigen Receptor-Natural Killer Cells: The Future of Cancer Immunotherapy

Cited by 21 publications

References 6 publications

Natural Killer Cells in Immunotherapy: Are We Nearly There?

Natural Killer Cells in Immunotherapy: Are We Nearly There?

CAR T Cell Therapy for Pediatric Brain Tumors

Innovative CAR-T Cell Therapy for Solid Tumor; Current Duel between CAR-T Spear and Tumor Shield

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