The human natural killer cytotoxic cell line NK-92, once armed with a murine CD16 receptor, represents a convenient cellular tool for the screening of mouse mAbs according to their ADCC potential

Clémenceau, Béatrice; Vivien, Régine; Pellat, C.; Foss, Michael; Thibault, Gilles; Vié, Henri

doi:10.4161/mabs.25077

Cited by 38 publications

(36 citation statements)

References 15 publications

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“…NK-92, which is phenotypically CD16-negative, readily mediates ADCC in the presence of a suitable IgG antibody when engineered to express FcγRIIIa (27, 97, 100). This has sparked efforts to clinically develop genetically modified NK-92 cells that harbor the high affinity V158 variant of CD16 (termed haNK) in combination with antibodies of IgG1 isotype (32, 97).…”

Section: Car-engineered Nk-92 Cells Exhibit Antibody-dependent Cell-mmentioning

confidence: 99%

Chimeric Antigen Receptor-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Targeted Elimination of Cancer Cells and Induction of Protective Antitumor Immunity

et al. 2017

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Significant progress has been made in recent years toward realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells and have the intrinsic potential to extravasate and reach their targets in almost all body tissues. In addition to donor-derived primary NK cells, also the established NK cell line NK-92 is being developed for adoptive immunotherapy, and general safety of infusion of irradiated NK-92 cells has been established in phase I clinical trials with clinical responses observed in some of the cancer patients treated. To enhance their therapeutic utility, NK-92 cells have been modified to express chimeric antigen receptors (CARs) composed of a tumor-specific single chain fragment variable antibody fragment fused via hinge and transmembrane regions to intracellular signaling moieties such as CD3ζ or composite signaling domains containing a costimulatory protein together with CD3ζ. CAR-mediated activation of NK cells then bypasses inhibitory signals and overcomes NK resistance of tumor cells. In contrast to primary NK cells, CAR-engineered NK-92 cell lines suitable for clinical development can be established from molecularly and functionally well-characterized single cell clones following good manufacturing practice-compliant procedures. In preclinical in vitro and in vivo models, potent antitumor activity of NK-92 variants targeted to differentiation antigens expressed by hematologic malignancies, and overexpressed or mutated self-antigens associated with solid tumors has been found, encouraging further development of CAR-engineered NK-92 cells. Importantly, in syngeneic mouse tumor models, induction of endogenous antitumor immunity after treatment with CAR-expressing NK-92 cells has been demonstrated, resulting in cures and long-lasting immunological memory protecting against tumor rechallenge at distant sites. Here, we summarize the current status and future prospects of CAR-engineered NK-92 cells as off-the-shelf cellular therapeutics, with special emphasis on ErbB2 (HER2)-specific NK-92 cells that are approaching clinical application.

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Section: Car-engineered Nk-92 Cells Exhibit Antibody-dependent Cell-mmentioning

confidence: 99%

Chimeric Antigen Receptor-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Targeted Elimination of Cancer Cells and Induction of Protective Antitumor Immunity

et al. 2017

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“…Binding of anti-CD20-RLI ICK to FcγRIIIa (CD16a) expressed on the surface of NK-92-CD16 + cells 38 was also studied and compared with that of RTX. It was evaluated by measuring the inhibition of the binding of the FITC-conjugated anti-CD16a mAb 3G8 to NK-92-CD16 + cells.…”

Section: Characterization Of the Anti-cd20-rli Ick Ick Construction Imentioning

confidence: 99%

Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma in SCID mouse

Vincent¹,

Teppaz²,

Lajoie³

et al. 2014

mAbs

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International audienceRituximab (RTX), a chimeric IgG1 monoclonal antibody directed against the CD20 antigen, has revolutionized the treatment of B-cell malignancies. Nevertheless, the relapsed/refractory rates are still high. One strategy to increase the clinical effectiveness of RTX is based on antibody-cytokine fusion protein (immunocytokine; ICK) vectorizing together at the tumor site the antibody effector activities and the cytokine co-signal required for the generation of cytotoxic cellular immunity. Such ICKs linking various antibody formats to interleukin (IL)-2 are currently being investigated in clinical trials and have shown promising results in cancer therapies. IL-15, a structurally-related cytokine, is now considered as having a better potential than IL-2 in antitumor immunotherapeutic strategies. We have previously engineered the fusion protein RLI, linking a soluble form of human IL-15Rα-sushi+ domain to human IL-15. Compared with IL-15, RLI displayed better biological activities in vitro and higher antitumor effects in vivo in murine and human cancer models. In this study, we investigated the advantages of fusing RLI to RTX. Anti-CD20-RLI kept its binding capacity to CD20, CD16 and IL-15 receptor and therefore fully retained both antibody effector functions (ADCC and CDC), and the cytokine potential of RLI. In a severe combined immunodeficiency (SCID) mouse model of disseminated residual lymphoma, anti-CD20-RLI was found to induce long-term survival of 90% of mice up to at least 120 days whereas RLI and RTX, alone or in combination, just delayed the disease onset (100% of death at 28, 40 and 51 days respectively). These findings suggest that such ICK could improve the clinical efficacy of RTX, particularly in patients with refractory B-cell lymphoma.Keywords: interleukin-15, CD20, Rituximab, immunocytokine, cancer therapy, lymphoma, B cell malignancie

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“…For instance, NK cells have short life span and lack clonal expansion. Meanwhile, targeted killing depends on the immune checkpoints, and the detected antigens are nonspecific . Further research will have to identify unique targets, promote the effective therapeutic immune responses to MM, and avoid side effects.…”

Section: Resultsmentioning

confidence: 99%

Natural killer cell immunotherapy against multiple myeloma: Progress and possibilities

Liu

Jin

Sattar

et al. 2018

Journal of Leukocyte Biology

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Multiple myeloma (MM) is a complex aggressive mature B-cell malignancy. Although with the wide application of chemotherapy drugs, it remains incurable and the vast majority of patients relapse. Natural killer (NK) cells, also known as CD56 CD3 large granular lymphocytes, are cytotoxic innate immune cells against MM without prior sensitization steps. NK cell-based immunotherapy is extensively promising in a wide range of clinical settings. It is worthy of note that some novel drugs such as monoclonal antibodies (mAbs), proteasome inhibitors (PIs), and immunomodulators (IMiDs) directly or indirectly activate NK cells to enhance their antitumor activity, and the combined regimens significantly improve the prognosis of MM patients. In this review, we summarize recent findings that support a role for NK cells in the pathogenesis of MM and outline innovative approaches in the implementation of NK cell-based immunotherapy against MM.

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The human natural killer cytotoxic cell line NK-92, once armed with a murine CD16 receptor, represents a convenient cellular tool for the screening of mouse mAbs according to their ADCC potential

Cited by 38 publications

References 15 publications

Chimeric Antigen Receptor-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Targeted Elimination of Cancer Cells and Induction of Protective Antitumor Immunity

Chimeric Antigen Receptor-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Targeted Elimination of Cancer Cells and Induction of Protective Antitumor Immunity

Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma in SCID mouse

Natural killer cell immunotherapy against multiple myeloma: Progress and possibilities

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