FcεRIγ-negative NK cells persist in vivo and enhance efficacy of therapeutic monoclonal antibodies in multiple myeloma

Bigley, Austin B.; Spade, Shanae; Agha, Nadia H.; Biswas, Sujit; Tang, Su-Ni; Malik, Muhammad H.; Dai, Lu; Masoumi, Shalaleh; Patiño-Escobar, Bonell; Hale, Martina; DiPierro, Guy; Martell, Ronald; Hann, Byron; Shah, Nina; Wiita, Arun P.; Liu, Xinli

doi:10.1182/bloodadvances.2020002440

Cited by 25 publications

(23 citation statements)

References 22 publications

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“…Although these cells express a lower amount of natural cytotoxic receptors and thus show weak responsiveness toward the K562 tumor cell line compared to FcϵRIg+ NK cells (74), they display an increased activity through Ab-dependent stimulation (74) and ADCC (75). Recently, a method to ex vivo expand these so-called "g-NK" cells has been published (77). Although the expansion is only possible from previously HCMVinfected donors, the resulting cells possess some interesting features.…”

Section: Making Highly Active Natural Killer Cells For Therapymentioning

confidence: 99%

From CD16a Biology to Antibody-Dependent Cell-Mediated Cytotoxicity Improvement

Coënon

Martín

2022

Front. Immunol.

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Antibody-dependent cell-mediated cytotoxicity (ADCC) is a potent cytotoxic mechanism that is mainly mediated in humans by natural killer (NK) cells. ADCC mediates the clinical benefit of several widely used cytolytic monoclonal antibodies (mAbs), and increasing its efficacy would improve cancer immunotherapy. CD16a is a receptor for the Fc portion of IgGs and is responsible to trigger NK cell-mediated ADCC. The knowledge of the mechanism of action of CD16a gave rise to several strategies to improve ADCC, by working on either the mAbs or the NK cell. In this review, we give an overview of CD16a biology and describe the latest strategies employed to improve antibody-dependent NK cell cytotoxicity.

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Section: Making Highly Active Natural Killer Cells For Therapymentioning

confidence: 99%

From CD16a Biology to Antibody-Dependent Cell-Mediated Cytotoxicity Improvement

Coënon

Martín

2022

Front. Immunol.

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“…The common gamma chain (γc) receptor family cytokines, including IL-2, IL-15, and IL-21, are required for the generation, persistence, and homeostasis of adaptive NK cells ( 57 ). IL-2 was first discovered as a T cell growth factor in 1976 and was later found to have various pleiotropic properties, including the ability to augment the cytolytic activities of NK cells and cytotoxic T cells.…”

Section: Functional Characteristics Of Adaptive Nk Cellsmentioning

confidence: 99%

“…Moreover, 5 of the 7 mice eliminated the burden of myeloma, with a survival rate of up to 100% after 60 days. Interestingly, the persistence of expanded g - NK cells is detected in the blood, spleen and, BM relative to that of c-NK cells in the MM model ( 57 ).…”

Section: Clinical Relevance Of Adaptive Nk Cellsmentioning

confidence: 99%

Biology and Clinical Relevance of HCMV-Associated Adaptive NK Cells

et al. 2022

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Natural killer (NK) cells are an important component of the innate immune system due to their strong ability to kill virally infected or transformed cells without prior exposure to the antigen (Ag). However, the biology of human NK (hNK) cells has largely remained elusive. Recent advances have characterized several novel hNK subsets. Among them, adaptive NK cells demonstrate an intriguing specialized antibody (Ab)-dependent response and several adaptive immune features. Most adaptive NK cells express a higher level of NKG2C but lack an intracellular signaling adaptor, FcϵRIγ (hereafter abbreviated as FcRγ). The specific expression pattern of these genes, with other signature genes, is the result of a specific epigenetic modification. The expansion of adaptive NK cells in vivo has been documented in various viral infections, while the frequency of adaptive NK cells among peripheral blood mononuclear cells correlates with improved prognosis of monoclonal Ab treatment against leukemia. This review summarizes the discovery and signature phenotype of adaptive NK cells. We also discuss the reported association between adaptive NK cells and pathological conditions. Finally, we briefly highlight the application of adaptive NK cells in adoptive cell therapy against cancer.

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“…Equally, FcεRIγ-deficient NK (g-NK) cells are a rare group of cells originated from CMV-seropositive subjects (CD38low and SLAMF7low). An experimentation demonstrated that with respect to traditional NK cells, ex vivo g-NK cells, in combined administration with daratumumab, presented an augmented cytotoxicity against MM cells [ 152 ].…”

Section: Acute Leukemiamentioning

confidence: 99%

Harnessing Unconventional T Cells and Innate Lymphoid Cells to Prevent and Treat Hematological Malignancies: Prospects for New Immunotherapy

et al. 2022

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Unconventional T cells and innate lymphoid cells (ILCs) make up a heterogeneous set of cells that characteristically show prompt responses toward specific antigens. Unconventional T cells recognize non-peptide antigens, which are bound and presented by diverse non-polymorphic antigen-presenting molecules and comprise γδ T cells, MR1-restricted mucosal-associated invariant T cells (MAITs), and natural killer T cells (NKTs). On the other hand, ILCs lack antigen-specific receptors and act as the innate counterpart to the T lymphocytes found in the adaptive immune response. The alteration of unconventional T cells and ILCs in frequency and functionality is correlated with the onset of several autoimmune diseases, allergy, inflammation, and tumor. However, depending on the physio-pathological framework, unconventional T cells may exhibit either protective or pathogenic activity in a range of neoplastic diseases. Nonetheless, experimental models and clinical studies have displayed that some unconventional T cells are potential therapeutic targets, as well as prognostic and diagnostic markers. In fact, cell-mediated immune response in tumors has become the focus in immunotherapy against neoplastic disease. This review concentrates on the present knowledge concerning the function of unconventional T cell sets in the antitumor immune response in hematological malignancies, such as acute and chronic leukemia, multiple myeloma, and lymphoproliferative disorders. Moreover, we discuss the possibility that modulating the activity of unconventional T cells could be useful in the treatment of hematological neoplasms, in the prevention of specific conditions (such as graft versus host disease), and in the formulation of an effective anticancer vaccine therapy. The exact knowledge of the role of these cells could represent the prerequisite for the creation of a new form of immunotherapy for hematological neoplasms.

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FcεRIγ-negative NK cells persist in vivo and enhance efficacy of therapeutic monoclonal antibodies in multiple myeloma

Cited by 25 publications

References 22 publications

From CD16a Biology to Antibody-Dependent Cell-Mediated Cytotoxicity Improvement

From CD16a Biology to Antibody-Dependent Cell-Mediated Cytotoxicity Improvement

Biology and Clinical Relevance of HCMV-Associated Adaptive NK Cells

Harnessing Unconventional T Cells and Innate Lymphoid Cells to Prevent and Treat Hematological Malignancies: Prospects for New Immunotherapy

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