Oncotarget

Research Papers:

Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer

Julie Jacobs, Karen Zwaenepoel, Christian Rolfo _, Jolien Van den Bossche, Christophe Deben, Karen Silence, Christophe Hermans, Evelien Smits, Paul Van Schil, Filip Lardon, Vanessa Deschoolmeester and Patrick Pauwels

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:13462-13475. https://doi.org/10.18632/oncotarget.3880

Metrics: PDF 1526 views  |   HTML 1731 views  |   ?  


Abstract

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

Correspondence to:

Christian Rolfo, email:

Keywords: CD70, NSCLC, immunotherapy, targeted therapies

Received: February 03, 2015 Accepted: April 03, 2015 Published: April 19, 2015

Abstract

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 3880