Anti-Epidermal Growth Factor Vaccine Antibodies Enhance the Efficacy of Tyrosine Kinase Inhibitors and Delay the Emergence of Resistance in EGFR Mutant Lung Cancer Cells

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
Jordi Codony-ServatRafael Rosell

Abstract

Mutations in EGFR correlate with impaired response to immune checkpoint inhibitors and the development of novel immunotherapeutic approaches for EGFR mutant NSCLC is of particular interest. Immunization against epidermal growth factor (EGF) has shown efficacy in a phase III trial including unselected NSCLC patients, but little was known about the mechanisms involved in the effects of the anti-EGF antibodies generated by vaccination (anti-EGF VacAbs) or their activity in tumor cells with EGFR mutations. The EGFR-mutant, NSCLC cell lines H1975, and PC9, together with several gefitinib and osimertinib-resistant cells derived from PC9, were treated with anti-EGF VacAbs and/or EGFR tyrosine kinase inhibitors (TKIs). Cell viability was analyzed by proliferation assays, cell cycle by fluorescence-activated cell sorting analysis, and levels of RNA and proteins by quantitative retro-transcription polymerase chain reaction and Western blotting. Anti-EGF VacAbs generated in rabbits suppressed EGF-induced cell proliferation and cycle progression and inhibited downstream EGFR signaling in EGFR-mutant cells. Sera from patients immunized with an EGF vaccine were also able to block activation of EGFR effectors. In combination, the anti-EGF Vac...Continue Reading

Citations

Feb 15, 2019·Expert Opinion on Biological Therapy·Martyna FilipskaRafael Rosell
May 23, 2019·Expert Review of Respiratory Medicine·Alessia Spagnuolo, Cesare Gridelli
Oct 11, 2019·Current Opinion in Oncology·Rafael RosellOscar Arrieta
May 1, 2019·Cancers·Anubhab MukherjeeSudip Mukherjee
Jun 11, 2020·Cancers·Mariacarmela SantarpiaRafael Rosell
Aug 15, 2019·Expert Review of Respiratory Medicine·Niki KarachaliouRafael Rosell
Nov 11, 2019·Trends in Pharmacological Sciences·Salvador GuardiolaErnest Giralt
Jul 3, 2021·Frontiers in Oncology·Tania Crombet RamosAgustín Lage Dávila
Aug 20, 2021·Lung Cancer : Targets and Therapy·Aubhishek Zaman, Trever G Bivona

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