Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer
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Julie Jacobs1,2, Karen Zwaenepoel2, Christian Rolfo1,3,4, Jolien Van den Bossche1, Christophe Deben1, Karen Silence5, Christophe Hermans1,2, Evelien Smits1,6, Paul Van Schil7, Filip Lardon1, Vanessa Deschoolmeester1,2,* and Patrick Pauwels1,2,*
1 Center for Oncological Research Antwerp, Center for Oncological Research Antwerp (CORE), Antwerp University, Wilrijk, Belgium
2 Department of Pathology, Antwerp University Hospital, Edegem, Belgium
3 Department of Oncology, Antwerp University Hospital, Edegem, Belgium
4 Phase 1-Early Clinical Trials Unit, Antwerp University Hospital, Edegem, Belgium
5 arGEN-X BVBA, Ghent, Belgium
6 Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute, Antwerp University, Wilrijk, Belgium
7 Department of Thoracic and Vascular Surgery, Antwerp University Hospital, Edegem, Belgium
* These authors are co-senior authors
Christian Rolfo, email:
Keywords: CD70, NSCLC, immunotherapy, targeted therapies
Received: February 03, 2015 Accepted: April 03, 2015 Published: April 19, 2015
Although normally restricted to activated T and B cells and mature dendritic cells, constitutive expression of CD70, a member of the tumor necrosis family, has been described in both hematological and solid tumors, where it increases tumor cell and regulatory T cell survival by signaling through its receptor, CD27.
We have assessed the co-expression of CD70 and CD27 in non-small cell lung cancer (NSCLC) by immunohistochemistry to explore a correlation between expression of the protein and tumor histologic subtype, genetic aberrations and prognosis. Furthermore, we tested the ability of ARGX-110, a CD70-blocking antibody, to induce NK cell-mediated cytotoxicity.
Our results revealed CD70 expression on the surface of both primary and metastatic NSCLC tumor cells and in the tumor microenvironment. Moreover, CD27-expressing tumor infiltrating lymphocytes were found adjacent to the tumor cells, suggesting active CD70-mediated signaling. Finally, we have shown that ARGX-110, has potent cytotoxic effects on CD70+ NSCLC cell lines.
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