New Orders to an Old Soldier: Optimizing NK Cells for Adoptive Immunotherapy in Hematology

Gündüz, Mehmet; Atilla, Pinar Ataca; Atilla, Erden

doi:10.3390/biomedicines9091201

Cited by 4 publications

(4 citation statements)

References 115 publications

(123 reference statements)

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“…For that reason, several approaches emerged to enhance their antibody-dependent cellular cytotoxicity (ADCC). Some examples include the addition of checkpoint receptor blockers, antitumor monoclonal antibodies, bi-/tri-specific killer engagers (BiKEs and TriKEs), and the use of memory-type NK cells, which showed beneficial effects ( 51 ). Additionally, therapeutic applications recently explored the targeting of NK cells with memory functions, acquired during a previous activation ( 52 , 53 ).…”

Section: Autologous Nk Therapy Against Cancermentioning

confidence: 99%

“…Similar to the TGF-β mechanism, hypoxia affects NK cell cytotoxicity by decreasing the expression of activating receptors NKp46 and CD16. Hypoxia can also induce overexpression of the adenosine nucleotidase CD73, upregulate checkpoint molecules such as PD-L1, and down-regulate the activating ligand MICA on tumor cells ( 51 ).…”

Section: Targeting the Immunosuppressive Tumor Microenvironmentmentioning

confidence: 99%

“…Since NK possess several activation receptors, this concept was ideal to be used for the design of CAR-NK cells ( 130 ). These modifications intend to overcome the limitations of non-modified NK cells when facing tumor cells with genetic or epigenetic variations that bypass the NK immunological surveillance ( 51 , 58 ). CAR-NK cells can be produced from multiple sources (such as peripheral blood, cord blood, iPSCs, and NK-92 cell line), adopting the basic methods borrowed from CAR-T cell generation ( 131 ).…”

Section: Engineered Modification Of Nk Cellsmentioning

confidence: 99%

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The application of autologous cancer immunotherapies in the age of memory-NK cells

et al. 2023

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Cellular immunotherapy has revolutionized the oncology field, yielding improved results against hematological and solid malignancies. NK cells have become an attractive alternative due to their capacity to activate upon recognition of “stress” or “danger” signals independently of Major Histocompatibility Complex (MHC) engagement, thus making tumor cells a perfect target for NK cell-mediated cancer immunotherapy even as an allogeneic solution. While this allogeneic use is currently favored, the existence of a characterized memory function for NK cells (“memory-like” NK cells) advocates for an autologous approach, that would benefit from the allogeneic setting discoveries, but with added persistence and specificity. Still, both approaches struggle to exert a sustained and high anticancer effect in-vivo due to the immunosuppressive tumor micro-environment and the logistical challenges of cGMP production or clinical deployment. Novel approaches focused on the quality enhancement and the consistent large-scale production of highly activated therapeutic memory-like NK cells have yielded encouraging but still unconclusive results. This review provides an overview of NK biology as it relates to cancer immunotherapy and the challenge presented by solid tumors for therapeutic NKs. After contrasting the autologous and allogeneic NK approaches for solid cancer immunotherapy, this work will present the current scientific focus for the production of highly persistent and cytotoxic memory-like NK cells as well as the current issues with production methods as they apply to stress-sensitive immune cells. In conclusion, autologous NK cells for cancer immunotherapy appears to be a prime alternative for front line therapeutics but to be successful, it will be critical to establish comprehensives infrastructures allowing the production of extremely potent NK cells while constraining costs of production.

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Section: Autologous Nk Therapy Against Cancermentioning

confidence: 99%

Section: Targeting the Immunosuppressive Tumor Microenvironmentmentioning

confidence: 99%

Section: Engineered Modification Of Nk Cellsmentioning

confidence: 99%

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The application of autologous cancer immunotherapies in the age of memory-NK cells

et al. 2023

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“…NK cells are an important part of the body's immunity, which can recognize and kill tumor and virus-infected cells without prior sensitization, and coordinate and promote immune response [37,38]. NK cells secrete a variety of substances that promote immune efficacy and play a key role in eliminating harmful cells, such as tumor cells and virusinfected cells.…”

Section: Effect Of Mlds On the Nk Cell-killing Activity In Micementioning

confidence: 99%

Structural Characteristics and Immunomodulatory Effects of Melanoidins from Black Garlic

Song

Xue

Geng

et al. 2023

Foods

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Melanoidins are considered to have several biological activities. In this study, black garlic melanoidins (MLDs) were collected using ethanol solution extraction; 0%, 20%, and 40% ethanol solutions were used for chromatography. Three kinds of melanoidins were produced by macroporous resin, named MLD-0, MLD-20, and MLD-40. The molecular weight was determined, and the infrared and microscopic structures were studied. In addition, Balb/c mice were induced with cyclophosphamide (CTX) to establish an immune deficiency model to evaluate the immune efficacy of black garlic melanoidins (MLDs). The results showed that MLDs restored the proliferation and phagocytosis ability of macrophages, and the proliferation activity of B lymphocytes in the MD group was 63.32% (♀) and 58.11% (♂) higher than that in the CTX group, respectively. In addition, MLDs alleviated the abnormal expression of serum factors such as IFN-γ, IL-10, and TNF-α. 16SrDNA sequencing of intestinal fecal samples of mice showed that MLDs changed the structure and quantity of intestinal flora, and especially that the relative abundance of Bacteroidaceae was significantly increased. The relative abundance of Staphylococcaceae was significantly reduced. These results showed that MLDs improved the diversity of intestinal flora in mice, and improved the adverse state of immune organs and immune cells. The experiments confirm that black garlic melanoidins have potential value in immune activity, which provides an important basis for the development and utilization of melioidosis.

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Histone deacetylases (HDACs) as the promising immunotherapeutic targets for hematologic cancer treatment

Yang

Hu²,

Liu³

et al. 2023

European Journal of Medicinal Chemistry

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New Orders to an Old Soldier: Optimizing NK Cells for Adoptive Immunotherapy in Hematology

Cited by 4 publications

References 115 publications

The application of autologous cancer immunotherapies in the age of memory-NK cells

The application of autologous cancer immunotherapies in the age of memory-NK cells

Structural Characteristics and Immunomodulatory Effects of Melanoidins from Black Garlic

Histone deacetylases (HDACs) as the promising immunotherapeutic targets for hematologic cancer treatment

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