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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

(2017) ONCOTARGET . 8(43). p.74058-74067
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Abstract
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.
Keywords
non-small cell lung cancer, combination therapy, natural killer cell, CD70, chemotherapy, CD70 EXPRESSION, T-CELLS, IMMUNE ESCAPE, IMMUNOTHERAPY, CHEMOTHERAPY, APOPTOSIS, TARGET, LYMPHOCYTES, INCREASES, CARCINOMA

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Citation

Please use this url to cite or link to this publication:

Chicago
Jacobs, Julie, Vanessa Deschoolmeester, Christian Rolfo, Karen Zwaenepoel, Jolien Van den Bossche, Christophe Deben, Karen Silence, et al. 2017. “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.” Oncotarget 8 (43): 74058–74067.
APA
Jacobs, Julie, Deschoolmeester, V., Rolfo, C., Zwaenepoel, K., Van den Bossche, J., Deben, C., Silence, K., et al. (2017). 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. ONCOTARGET , 8(43), 74058–74067.
Vancouver
1.
Jacobs J, Deschoolmeester V, Rolfo C, Zwaenepoel K, Van den Bossche J, Deben C, et al. 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. ONCOTARGET . 2017;8(43):74058–67.
MLA
Jacobs, Julie, Vanessa Deschoolmeester, Christian Rolfo, et al. “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.” ONCOTARGET 8.43 (2017): 74058–74067. Print.
@article{8556487,
  abstract     = {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.},
  author       = {Jacobs, Julie and Deschoolmeester, Vanessa and Rolfo, Christian and Zwaenepoel, Karen and Van den Bossche, Jolien and Deben, Christophe and Silence, Karen and de Haard, Hans and Hermans, Christophe and Rottey, Sylvie and Vangestel, Christel and Lardon, Filip and Smits, Evelien and Pauwels, Patrick},
  issn         = {1949-2553},
  journal      = {ONCOTARGET },
  language     = {eng},
  number       = {43},
  pages        = {74058--74067},
  title        = {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},
  url          = {http://dx.doi.org/10.18632/oncotarget.18202},
  volume       = {8},
  year         = {2017},
}

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