Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-10-26

AUTHORS

Shauna M. Collins, Courtney E. Bakan, Gina D. Swartzel, Craig C. Hofmeister, Yvonne A. Efebera, Hakju Kwon, Gary C. Starling, David Ciarlariello, Shakthi Bhaskar, Edward L. Briercheck, Tiffany Hughes, Jianhua Yu, Audie Rice, Don M. Benson

ABSTRACT

Elotuzumab is a monoclonal antibody in development for multiple myeloma (MM) that targets CS1, a cell surface glycoprotein expressed on MM cells. In preclinical models, elotuzumab exerts anti-MM efficacy via natural killer (NK)-cell-mediated antibody-dependent cellular cytotoxicity (ADCC). CS1 is also expressed at lower levels on NK cells where it acts as an activating receptor. We hypothesized that elotuzumab may have additional mechanisms of action via ligation of CS1 on NK cells that complement ADCC activity. Herein, we show that elotuzumab appears to induce activation of NK cells by binding to NK cell CS1 which promotes cytotoxicity against CS1(+) MM cells but not against autologous CS1(+) NK cells. Elotuzumab may also promote CS1–CS1 interactions between NK cells and CS1(+) target cells to enhance cytotoxicity in a manner independent of ADCC. NK cell activation appears dependent on differential expression of the signaling intermediary EAT-2 which is present in NK cells but absent in primary, human MM cells. Taken together, these data suggest elotuzumab may enhance NK cell function directly and confer anti-MM efficacy by means beyond ADCC alone. More... »

PAGES

1841-1849

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00262-013-1493-8

DOI

http://dx.doi.org/10.1007/s00262-013-1493-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000948126

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24162108


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