Preclinical data on the combination of cisplatin and anti-CD70 therapy in non-small cell lung cancer as an excellent match in the era of combination therapy
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Julie Jacobs1,2, Vanessa Deschoolmeester1,2, Christian Rolfo3,4, Karen Zwaenepoel1,2, Jolien Van den Bossche1, Christophe Deben1,2, Karen Silence5, Hans de Haard5, Christophe Hermans1,2, Sylvie Rottey6, Christel Vangestel7, Filip Lardon1, Evelien Smits1,8,* and Patrick Pauwels1,2,*
1Center for Oncological Research, University of Antwerp, Antwerp, 2610 Wilrijk, Belgium
2Department of Pathology, Antwerp University Hospital, Antwerp, 2650 Edegem, Belgium
3Department of Oncology, Antwerp University Hospital, Antwerp, 2650, Edegem, Belgium
4Phase 1-Early Clinical Trials Unit, Antwerp University Hospital, Antwerp, 2650 Edegem, Belgium
5Argenx BVBA, Ghent, 9052 Zwijnaarde, Belgium
6Department of Medical Oncology, Ghent University Hospital, 9000 Ghent, Belgium
7Molecular Imaging Center Antwerp (MICA), University of Antwerp, Antwerp, 2610 Wilrijk, Belgium
8Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, 2610 Wilrijk, Belgium
Julie Jacobs, email: [email protected]
Keywords: non-small cell lung cancer, combination therapy, natural killer cell, CD70, chemotherapy
Received: February 15, 2017 Accepted: May 12, 2017 Published: May 23, 2017
In contrast to the negligible expression of the immunomodulating protein CD70 in normal tissue, we have demonstrated constitutive overexpression of CD70 on tumor cells in a subset of primary non-small cell lung cancer (NSCLC) biopsies. This can be exploited by CD70-targeting antibody-dependent cellular cytotoxicity (ADCC)-inducing antibodies. Early clinical trials of these antibodies have already shown promising results in CD70-positive malignancies.
In this study, we explored the potential of cisplatin to induce CD70 expression in NSCLC. Using real-time measurement tools, we also assessed the efficacy of a combination regimen with cisplatin and anti-CD70 therapy under normoxia and hypoxia. We identified an induction of CD70 expression on lung cancer cells upon low doses of cisplatin, independent of oxygen levels. More importantly, the use of cisplatin resulted in an enhanced ADCC-effect of anti-CD70 therapy. As such, this combination regimen led to a significant decrease in lung cancer cell survival cell survival, broadening the applicability the applicability of CD70-targeting therapy.
This is the first study that proves the potential of a combination therapy with cisplatin and CD70-targeting drugs in NSCLC. Based on our data, we postulate that this combination strategy is an interesting approach to increase tumor-specific cytotoxicity and reduce drug-related side effects.
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