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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.
Jacobs, Julie; Deschoolmeester, Vanessa; Rolfo, Christian; Zwaenepoel, Karen; Van den Bossche, Jolien; Deben, Christophe; Silence, Karen; de Haard, Hans; Hermans, Christophe; Rottey, Sylvie; Vangestel, Christel; Lardon, Filip; Smits, Evelien; Pauwels, Patrick.
Afiliação
  • Jacobs J; Center for Oncological Research, University of Antwerp, Antwerp, 2610 Wilrijk, Belgium.
  • Deschoolmeester V; Department of Pathology, Antwerp University Hospital, Antwerp, 2650 Edegem, Belgium.
  • Rolfo C; Center for Oncological Research, University of Antwerp, Antwerp, 2610 Wilrijk, Belgium.
  • Zwaenepoel K; Department of Pathology, Antwerp University Hospital, Antwerp, 2650 Edegem, Belgium.
  • Van den Bossche J; Department of Oncology, Antwerp University Hospital, Antwerp, 2650, Edegem, Belgium.
  • Deben C; Phase 1-Early Clinical Trials Unit, Antwerp University Hospital, Antwerp, 2650 Edegem, Belgium.
  • Silence K; Center for Oncological Research, University of Antwerp, Antwerp, 2610 Wilrijk, Belgium.
  • de Haard H; Department of Pathology, Antwerp University Hospital, Antwerp, 2650 Edegem, Belgium.
  • Hermans C; Center for Oncological Research, University of Antwerp, Antwerp, 2610 Wilrijk, Belgium.
  • Rottey S; Center for Oncological Research, University of Antwerp, Antwerp, 2610 Wilrijk, Belgium.
  • Vangestel C; Department of Pathology, Antwerp University Hospital, Antwerp, 2650 Edegem, Belgium.
  • Lardon F; Argenx BVBA, Ghent, 9052 Zwijnaarde, Belgium.
  • Smits E; Argenx BVBA, Ghent, 9052 Zwijnaarde, Belgium.
  • Pauwels P; Center for Oncological Research, University of Antwerp, Antwerp, 2610 Wilrijk, Belgium.
Oncotarget ; 8(43): 74058-74067, 2017 Sep 26.
Article em En | MEDLINE | ID: mdl-29088768
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2017 Tipo de documento: Article