Anti-epidermal growth factor vaccine antibodies increase the antitumor activity of kinase inhibitors in ALK and RET rearranged lung cancer cells
Por:
Codony-Servat, J, Garcia-Roman, S, Molina-Vila, MA, Bertran-Alamillo, J, Viteri, S, d'Hondt, E and Rosell, R
Publicada:
1 ene 2021
Ahead of Print:
23 oct 2020
Resumen:
Advanced NSCLC patients harboring EML4-ALK and CCDC6-RET rearrangements derive benefit from treatment with ALK and RET TKIs but not immune checkpoint inhibitors. New immunotherapeutic approaches, such as immunization against growth factors, can be of particular interest for combination treatment in these patients. Here, we investigated the effects of anti-EGF antibodies generated by vaccination (anti-EGF VacAbs), TKIs and combinations in EML4-ALK and CCDC6-RET NSCLC cell lines. We found that EGF and tumor growth factor alpha (TGFa) significantly decreased the antiproliferative activity of the RET inhibitor BLU-667 in CCDC6-RET cells and brigatinib, alectinib and crizotinib inEML4-ALK translocated cells. The addition of anti-EGF VacAbs reversed the effects of EGF and TGFa, potentiated the antitumor effects of the kinase inhibitors and delayed the appearance in vitro of resistant clones. Western blotting demonstrated that the combination of anti-EGF VacAbs with ALK or RET TKIs effectively suppressed EGFR downstream pathways in EML4-ALK translocated and CCDC6-RET cells, respectively. In conclusion, anti-EGF VacAbs significantly increased the antitumor activity of TKIs in ALK and RET-positive cell lines. Clinical trials of an EGF vaccine in combination with ALK and RET TKIs are warranted.
Filiaciones:
Codony-Servat, J:
Quiron Dexeus Univ Inst, Lab Oncol Pangaea Oncol SL, C Sabino Arana 5, Barcelona 08023, Spain
Garcia-Roman, S:
Quiron Dexeus Univ Inst, Lab Oncol Pangaea Oncol SL, C Sabino Arana 5, Barcelona 08023, Spain
Molina-Vila, MA:
Quiron Dexeus Univ Inst, Lab Oncol Pangaea Oncol SL, C Sabino Arana 5, Barcelona 08023, Spain
Bertran-Alamillo, J:
Quiron Dexeus Univ Inst, Lab Oncol Pangaea Oncol SL, C Sabino Arana 5, Barcelona 08023, Spain
Viteri, S:
Quiron Dexeus Univ Inst, Inst Oncol Dr Rosell IOR, Barcelona, Spain
d'Hondt, E:
In3Bio Europe Ltd, Aberdeen, Scotland
:
Quiron Dexeus Univ Inst, Inst Oncol Dr Rosell IOR, Barcelona, Spain
Catalan Inst Oncol, Badalona, Spain
Inst Invest Ciencies Germans Trias & Pujol, Badalona, Spain
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