Recent Advances to Augment NK Cell Cancer Immunotherapy Using Nanoparticles

Kim, Kwang S.; Kim, Dong Hwan; Kim, Dong Hyun

doi:10.3390/pharmaceutics13040525

Cited by 22 publications

(18 citation statements)

References 79 publications

(99 reference statements)

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“…NK cell immunotherapy is a promising therapeutic strategy; however, it is not without its limitations. As reviewed by Kim et al, several challenges remain regarding the efficacy of NK cell therapies, including increasing the activity, infiltration, and homing of NK cells, alongside promoting contact between NK cells and tumor cells [ 101 ]. The emergence of nanomedicine is an exciting and promising approach to resolving these aforementioned limitations, by aiding in the delivery and efficacy of NK cell therapies.…”

Section: The Future Of Nk Cell Therapies In Nsclcmentioning

confidence: 99%

Harnessing Natural Killer Cells in Non-Small Cell Lung Cancer

Russell

Conroy

Barr

2022

Cells

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Lung cancer is the leading cause of cancer-related deaths worldwide. There are two main subtypes: small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC). NSCLC accounts for 85% of lung cancer diagnoses. Early lung cancer very often has no specific symptoms, and many patients present with late stage disease. Despite the various treatments currently available, many patients experience tumor relapse or develop therapeutic resistance, highlighting the need for more effective therapies. The development of immunotherapies has revolutionized the cancer treatment landscape by enhancing the body’s own immune system to fight cancer. Natural killer (NK) cells are crucial anti-tumor immune cells, and their exclusion from the tumor microenvironment is associated with poorer survival. It is well established that NK cell frequencies and functions are impaired in NSCLC; thus, placing NK cell-based immunotherapies as a desirable therapeutic concept for this malignancy. Immunotherapies such as checkpoint inhibitors are transforming outcomes for NSCLC. This review explores the current treatment landscape for NSCLC, the role of NK cells and their dysfunction in the cancer setting, the advancement of NK cell therapies, and their future utility in NSCLC.

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Section: The Future Of Nk Cell Therapies In Nsclcmentioning

confidence: 99%

Harnessing Natural Killer Cells in Non-Small Cell Lung Cancer

Russell

Conroy

Barr

2022

Cells

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“…The use of CAR-NK cells in immunotherapy has yielded optimistic results, and provides several advantages over CAR-T cells, such as improved tolerance, reduced toxicity as well as multiple sources from which NK cells can be derived ( 151 ). However, CAR-NK cells are still associated with various technical and biological limitations, such as difficulties in CAR delivery into NK cells, the short lifespan of NK cells in the absence of additional cytokine treatment, the requirement for ex vivo expansion prior to infusion, low tumour infiltration capacity and reduced cytotoxicity in vivo ( 151 , 152 ). While strategies to engineer NK cells for improved performance are being studied, other areas of therapy are now also being explored for potential use in combination with established cancer therapy.…”

Section: Looking Beyond Targeting Nk Cell Receptors For Therapeutic Advancesmentioning

confidence: 99%

NK Cells in a Tug-of-War With Cancer: The Roles of Transcription Factors and Cytoskeleton

2021

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Natural killer (NK) cells are innate immune cells which play a key role in shaping the immune response against cancer. Initially hailed for their potential to recognise and eliminate tumour cells, their application has been greatly hindered by the immunosuppressive tumour microenvironment (TME) which suppresses NK functions (e.g., cytotoxicity). This dysfunctional state that is accompanied by phenotypic changes such as upregulation of inhibitory receptors and downregulation of activating receptors, forms the basis of what many researchers have referred to as ‘exhausted’ NK cells. However, there is no consensus on whether these phenotypes are sufficient to define an exhausted state of the NK cell. While recent advances in checkpoint inhibition appear to show promise in early-stage pre-clinical studies, much remains to be fully explored and understood in the context of the TME. The TME is where the NK cells are subjected to interaction with various cell types and soluble factors, which could exert an inhibitory effect on NK cytotoxicity. In this review, we provide an overview of the general markers of NK cell exhaustion viz, the surface activating and inhibitory receptors. We also highlight the potential role of T-box transcription factors in characterising such a dysfunctional state and discuss the often-overlooked mechanism of cell cytoskeletal dynamics in regulating NK cell function. These aspects may further contribute to NK exhaustion or NK revival in cancer and may open new avenues to explore cancer treatment strategies.

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“…Nanoparticles can be deployed to deliver therapeutic reagents such as antibodies, cytokines and genes, and are a promising combination strategy to enhance NK cell functionality. Multiple strategies are under development including inhibition of the immunosuppressive TME, improving migration and infiltration, and augmenting receptor-ligand activation response (reviewed in [ 131 ]). An example of TME modulation is the use of nanoscale liposomal polymeric gels to co-deliver a TGF-β inhibitor and IL-2 to the TME, resulting in decreased tumor growth and increased numbers of NK cells in the tumor of a B16 mouse melanoma model [ 132 ].…”

Section: Future Developments In Nk Cell Therapy For Melanomamentioning

confidence: 99%

Adoptive NK Cell Therapy: A Promising Treatment Prospect for Metastatic Melanoma

Vliet¹,

Georgoudaki²,

Raimo³

et al. 2021

Cancers

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Adoptive cell therapy (ACT) represents a promising alternative approach for patients with treatment-resistant metastatic melanoma. Lately, tumor infiltrating lymphocyte (TIL) therapy and chimeric antigen receptor (CAR)-T cell therapy have shown improved clinical outcome, compared to conventional chemotherapy or immunotherapy. Nevertheless, they are limited by immune escape of the tumor, cytokine release syndrome, and manufacturing challenges of autologous therapies. Conversely, the clinical use of Natural Killer (NK) cells has demonstrated a favorable clinical safety profile with minimal toxicities, providing an encouraging treatment alternative. Unlike T cells, NK cells are activated, amongst other mechanisms, by the downregulation of HLA class I molecules, thereby overcoming the hurdle of tumor immune escape. However, impairment of NK cell function has been observed in melanoma patients, resulting in deteriorated natural defense. To overcome this limitation, “activated” autologous or allogeneic NK cells have been infused into melanoma patients in early clinical trials, showing encouraging clinical benefit. Furthermore, as several NK cell-based therapeutics are being developed for different cancers, an emerging variety of approaches to increase migration and infiltration of adoptively transferred NK cells towards solid tumors is under preclinical investigation. These developments point to adoptive NK cell therapy as a highly promising treatment for metastatic melanoma in the future.

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Recent Advances to Augment NK Cell Cancer Immunotherapy Using Nanoparticles

Cited by 22 publications

References 79 publications

Harnessing Natural Killer Cells in Non-Small Cell Lung Cancer

Harnessing Natural Killer Cells in Non-Small Cell Lung Cancer

NK Cells in a Tug-of-War With Cancer: The Roles of Transcription Factors and Cytoskeleton

Adoptive NK Cell Therapy: A Promising Treatment Prospect for Metastatic Melanoma

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