The CD38 low natural killer cell line KHYG1 transiently expressing CD16 F158V in combination with daratumumab targets multiple myeloma cells with minimal effector NK cell fratricide

Document Type

Article

Publication Date

3-1-2020

Institution/Department

Maine Medical Center Research Institute

Journal Title

Cancer immunology, immunotherapy : CII

MeSH Headings

ADP-ribosyl Cyclase 1, Animals, Antibodies, Monoclonal, Cell Line, Tumor, Humans, Killer Cells, Natural, Mice, Multiple Myeloma, Receptors, IgG

Abstract

Multiple myeloma (MM) is a clonal plasma cell malignancy typically associated with the high and uniform expression of the CD38 transmembrane glycoprotein. Daratumumab is a humanized IgG1κ CD38 monoclonal antibody (MoAb) which has demonstrated impressive single agent activity even in relapsed refractory MM patients as well as strong synergy with other anti-MM drugs. Natural Killer (NK) cells are cytotoxic immune effector cells that mediate in vivo tumour immunosurveillance. NK cells also play an important role during MoAb therapy by inducing antibody dependent cellular cytotoxicity (ADCC) via their FcγRIII (CD16) receptor. Furthermore, 15% of the population express a naturally occurring variant of CD16 harbouring a single-point polymorphism (F158V). However, the contribution of NK cells to the efficacy of daratumumab remains debatable as clinical data clearly indicate the rapid depletion of CD38

ISSN

1432-0851

First Page

421

Last Page

434

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