Journal article
Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis
J Stagg, U Divisekera, N McLaughlin, J Sharkey, S Pommey, D Denoyer, KM Dwyer, MJ Smyth
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2010
Abstract
Extracellular adenosine is a potent immunosuppressor that accumulates during tumor growth. We performed proof-of-concept studies investigating the therapeutic potential and mechanism of action of monoclonal antibody (mAb)-based therapy against CD73, an ecto-enzyme overexpressed on breast-cancer cells that catalyzes the dephosphorylation of adenosine monophosphates into adenosine. We showed that anti-CD73 mAb therapy significantly delayed primary 4T1.2 and E0771 tumor growth in immune-competent mice and significantly inhibited the development of spontaneous 4T1.2 lung metastases. Notably, anti-CD73 mAb therapy was essentially dependent on the induction of adaptive anti-tumor immune responses...
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Awarded by US Department of Defense Breast Cancer
Funding Acknowledgements
We thank Michelle Stirling for breeding and maintenance of the mice in this study and Dr. Andreas Moller for critical review of our manuscript. This work was supported by a US Department of Defense Breast Cancer Concept Award (W81XWH-08-1-0634) and the Susan G. Komen Breast Cancer Foundation. J. S. is supported by a Canadian Institutes of Health Research (CIHR) Fellowship. M. J. S is supported by a National Health and Medical Research Council of Australia Fellowship and Program Grant.