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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
Cancer immunology, immunotherapy : CII
  • Subhashis Sarkar
  • Sachin K S Chauhan
  • John Daly
  • Alessandro Natoni
  • Heather Fairfield, Maine Medical Center
  • Robert Henderson
  • Emma Nolan
  • Dawn Swan
  • Jinsong Hu
  • Michaela R Reagan, Maine Medical Center
  • Michael O'Dwyer
Document Type
Article
Publication Date
3-1-2020
Institution/Department
Maine Medical Center Research Institute
Disciplines
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

Citation Information
Subhashis Sarkar, Sachin K S Chauhan, John Daly, Alessandro Natoni, et al.. "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" Cancer immunology, immunotherapy : CII Vol. 69 Iss. 3 (2020) p. 421 - 434 ISSN: 1432-0851
Available at: http://works.bepress.com/michaela-reagan/4/