Induction of natural killer antibody-dependent cell cytotoxicity and of clinical activity of cetuximab plus avelumab in non-small cell lung cancer
| العنوان: | Induction of natural killer antibody-dependent cell cytotoxicity and of clinical activity of cetuximab plus avelumab in non-small cell lung cancer |
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| المؤلفون: | Maria Lucia Iacovino, Alessandro Morabito, Mario Capasso, Vincenzo Sforza, Vincenzo Famiglietti, Evaristo Maiello, Flora Cimmino, Giuseppe Viscardi, Morena Fasano, Achille Iolascon, Carminia Maria Della Corte, Giusi Barra, Francesca Sparano, Raimondo Di Liello, Vincenza Ciaramella, Fernando Paragliola, Fortunato Ciardiello, Floriana Morgillo |
| المساهمون: | Fasano, M., Della Corte, C. M., Di Liello, R., Barra, G., Sparano, F., Viscardi, G., Iacovino, M. L., Paragliola, F., Famiglietti, V., Ciaramella, V., Cimmino, F., Capasso, M., Iolascon, A., Sforza, V., Morabito, A., Maiello, E., Ciardiello, F., Morgillo, F. |
| المصدر: | ESMO Open ESMO Open, Vol 5, Iss 5 (2020) |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cancer Research, Lung Neoplasms, NK cells, Antibodies, Monoclonal, Humanized, NSCLC, lcsh:RC254-282, Avelumab, chemistry.chemical_compound, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Lactate dehydrogenase, cetuximab, Humans, Medicine, NK cell, Progression-free survival, Cytotoxicity, Lung cancer, neoplasms, Original Research, Antibody-dependent cell-mediated cytotoxicity, Cetuximab, business.industry, Antibody-Dependent Cell Cytotoxicity, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Killer Cells, Natural, Oncology, chemistry, Immunoglobulin G, Cancer research, avelumab, ADCC, business, Ex vivo, medicine.drug |
| الوصف: | Background Antibody-dependent cell-mediated cytotoxicity (ADCC) may mediate antitumour activity of IgG1-isotype monoclonal antibody (mAb), suggesting as potential treatment combination of IgG1-mAbs, anti-epidermal growth factor receptor cetuximab and anti-programmed death-ligand-1 avelumab. Methods We evaluated ADCC induction in lung cancer cells by lactate dehydrogenase (LDH) release assay. Antitumour activity and safety of cetuximab plus avelumab were explored in a single-arm proof-of-concept study in pre-treated non-small cell lung cancer (NSCLC) patients (pt) (Cetuximab-AVElumab-lung, CAVE-Lung). Search for predictive biomarkers of response was done. Results Avelumab plus cetuximab induced ADCC in NSCLC cells in vitro in presence of natural killers (NK) from healthy donors (HD) or NSCLC pt, as effectors. Sixteen relapsed NSCLC pt were treated with avelumab plus cetuximab. Antitumour activity was observed in 6/16 pt, defined by progression free survival (PFS) ≥8 months, with 4 of them still on treatment at data lock time (range, 14–19 months). Of note, 3/6 responders had received as previous line anti-programmed death-1 therapy. In responders, clinical benefit was accompanied by significant increase in LDH release over baseline at the first radiological evaluation (8 weeks) (p=0.01) and by early skin toxicity; while in the 10 non-responders, that had PFS ≤5 months, LDH release tends to reduce. Baseline circulating DNA levels were higher in non-responders compared with responders and HD (p=0.026) and decrease in responders during therapy. Mutations in DNA damage responsive family genes were found in responders. Conclusion Cetuximab and avelumab activates NSCLC pt NK cells. Ex vivo evaluation of ADCC, circulating DNA levels and early skin toxicity may predict response to cetuximab plus avelumab in NSCLC. EUDRACT 2017-004195-58 |
| تدمد: | 2059-7029 2017-0041 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a59405b9338f5e9a3eecd89070dc583bTest https://doi.org/10.1136/esmoopen-2020-000753Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a59405b9338f5e9a3eecd89070dc583b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20597029 20170041 |
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