American journal of translational research 2015-01-01

CD39 is a promising therapeutic antibody target for the treatment of soft tissue sarcoma.

Gregory M Hayes, Belinda Cairns, Zoia Levashova, Lawrence Chinn, Myra Perez, Jan-Willem Theunissen, Sindy Liao-Chan, Abel Bermudez, Mark R Flory, Karl J Schweighofer, Edward H van der Horst

Index: Am. J. Transl. Res. 7(6) , 1181-8, (2015)

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Abstract

Soft tissue sarcoma (STS) is a heterogenous tumor arising from the embryonic mesoderm represented by approximately 50 histological subtypes. Effective therapeutic intervention is lacking for recurrent, late stage and metastatic disease. CD39, a cell-surface ectonucleotidase, has previously been shown to be upregulated in hematological malignancies and various epithelial tumors, but not in STS. Here, we show by mass spectrometry and immunohistochemistry that CD39 is highly expressed in primary patient sarcoma samples. Moreover, CD39 nucleotidase activity is enhanced in fibrosarcoma compared with normal control cells. We demonstrate that an inhibitory monoclonal anti-CD39 antibody, abrogates CD39 enzymatic activity significantly and prolongs survival in a lethal metastatic patient-derived sarcoma model. Taken together, the data suggest CD39 is a novel therapeutic target for the treatment of STS.