Abstract 1524: CD137 (4-1BB) engagement fine-tunes the synergistic IL-15- and IL-21-driven NK cell proliferation

Vidard, Laurent; Dureuil-Sizaire, Christine; Baudhuin, Jérémy; Vescovi, Lionel; Durand, Laurence; Sierra, Véronique; Parmantier, Eric

doi:10.1158/1538-7445.sabcs18-1524

Cited by 2 publications

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“…Blockade of PD1/PD-L1 interaction can enhance NK cell activity both in vitro as well as in animal models due to an enhanced ADCC-induced anti-tumor function leading to an increased tumor control. Moreover, NK cells play also a role in response to treatment with agonistic anti-CD137/4-1BB antibodies (Abs) (110). CD137 is expressed on primed NK cells, which upon ligation provides a powerful costimulatory signal (111).…”

Section: Different Strategies To Revert Immune Surveillance By Nk Cel...mentioning

confidence: 99%

Underlying mechanisms of evasion from NK cells as rationale for improvement of NK cell-based immunotherapies

Seliger

Koehl

2022

Front. Immunol.

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Natural killer (NK) cells belong to the family of innate immune cells with the capacity to recognize and kill tumor cells. Different phenotypes and functional properties of NK cells have been described in tumor patients, which could be shaped by the tumor microenvironment. The discovery of HLA class I-specific inhibitory receptors controlling NK cell activity paved the way to the fundamental concept of modulating immune responses that are regulated by an array of inhibitory receptors, and emphasized the importance to explore the potential of NK cells in cancer therapy. Although a whole range of NK cell-based approaches are currently being developed, there are still major challenges that need to be overcome for improved efficacy of these therapies. These include escape of tumor cells from NK cell recognition due to their expression of inhibitory molecules, immune suppressive signals of NK cells, reduced NK cell infiltration of tumors, an immune suppressive micromilieu and limited in vivo persistence of NK cells. Therefore, this review provides an overview about the NK cell biology, alterations of NK cell activities, changes in tumor cells and the tumor microenvironment contributing to immune escape or immune surveillance by NK cells and their underlying molecular mechanisms as well as the current status and novel aspects of NK cell-based therapeutic strategies including their genetic engineering and their combination with conventional treatment options to overcome tumor-mediated evasion strategies and improve therapy efficacy.

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Section: Different Strategies To Revert Immune Surveillance By Nk Cel...mentioning

confidence: 99%

Underlying mechanisms of evasion from NK cells as rationale for improvement of NK cell-based immunotherapies

Seliger

Koehl

2022

Front. Immunol.

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Cellular therapy: Adoptive immunotherapy with expanded natural killer cells

Lee

2019

Immunological Reviews

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Adoptive immunotherapy with natural killer cells was pioneered 30 years ago in human clinical trials with the development of cytokine‐induced killer cells—unfractionated peripheral blood mononuclear cell (PBMC) populations activated overnight with IL‐2. Higher doses were subsequently made possible through the advent of steady‐state apheresis, allowing the collection of PBMC numbers equivalent to an entire adult blood volume, and increased purity made feasible through magnetic CD3‐depletion and/or CD56‐selection methods. Still, these approaches rarely achieved clinical dosing above a single infusion of 108 NK cells/kg, except with substantial donor‐recipient size mismatch (eg, parents donating cells to children). To address this shortcoming, leukemia cell lines with NK cell‐like function or ex vivo expansion approaches centered on the homeostatic cytokine IL‐15 were developed. Here, we describe the development of an ex vivo expansion system based on a feeder cell expressing membrane‐bound IL‐21 that enables log‐phase growth of primary NK cells for many weeks without inducing senescence, and describe the biology, correlative science, and translation to clinical trials for patients with leukemia, brain tumors, and solid tumors.

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Abstract 1524: CD137 (4-1BB) engagement fine-tunes the synergistic IL-15- and IL-21-driven NK cell proliferation

Cited by 2 publications

References 0 publications

Underlying mechanisms of evasion from NK cells as rationale for improvement of NK cell-based immunotherapies

Underlying mechanisms of evasion from NK cells as rationale for improvement of NK cell-based immunotherapies

Cellular therapy: Adoptive immunotherapy with expanded natural killer cells

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