60P - Antitumor effects of EGF-pathway immunization in NSCLC (60P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Palliative and Supportive Care
Presenter JORDI Codony-Servat
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors J. Codony-Servat1, S. García-Roman2, M.A. Molina-Vila2, J. Bertran-Alamillo2, A. Giménez-Capitán1, N. Karachaliou1, E. D'Hondt3, R. Rosell4
  • 1Laboratory Of Oncology - Pangaea Oncology, Quirón-Dexeus University Institute, 08028 - Barcelona/ES
  • 2Laboratory Of Oncology - Pangaea Oncology, Quirón-Dexeus University Institute, 08023 - Barcelona/ES
  • 3Oncology, Bioven, London/GB
  • 4Cancer Biology & Precision Medicine Program, Germans Trias I Pujol Science Inst., Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, 8916 - Badalona/ES

Abstract

Background

Immunization against Epidermal Growth Factor (EGF) has demostrated clinical efficacy in a phase III trial including unselected non-small cell lung cancer (NSCLC) patients. We analyzed if anti-EGF antibodies generated by vaccination (anti-EGF VacAbs) showed antitumor activity in EGFR-mutant, Kras-mutant and Anaplastic Lymphoma Kinase (ALK)-translocated NSCLC cell lines, alone or in combination with tyrosine kinase inhibitors (TKI).

Methods

The EGFR-mutant NSCLC cell line H1975 and osimertinib-resistant cell line (PC9-OR4), Kras-mutant cells A549 and H23 and Alk-translocated cells H3122 and H2228 were treated with anti-EGF VacAbs and the EGFR-mut cells treated also in combination with EGFR TKIs Erlotinib or Afatinib. Cell viability was analyzed by MTT, and apoptosis and cell cycle by fluorescence-activated cell sorting analysis (FACS). Changes of total and phosphorylated proteins were determined by Western blot.

Results

Anti-EGF VacAbs suppressed EGF-induced cell viability and inhibited downstream EGFR signaling. In combination, in EGFR-mutant cells, the anti-EGF VacAbs significantly enhanced the antitumor activity of all EGFR-TKIs tested, suppressed Erk 1/2 phosphorylayion, blocked the activation of STAT3 and downregulated the expression of proteins related to EGFR resistance, such as AXL. Also, they arrested cell cycle progression and increased apoptosis. Finally, anti-EGF VacAbs significantly delayed the emergence in vitro of EGFR TKI resistant clones.

Conclusions

Anti-EGF VacAbs decreased cell viability and inhibited the expression of several EGFR-pathway related proteins. Also, they potentiate the effects of EGFR TKIs and prevent the emergence of resistance in EGFR-mut NSCLC cells. A Phase III clinical trial of anti-EGF vaccination in EGFR wt NSCLC patients is currently ongoing. In addition, a Phase I trial of the EGF vaccine, in combination with EGFR TKIs, will be initiated.

Clinical trial identification

Legal entity responsible for the study

Pangaea Oncology

Funding

Bioven

Disclosure

All authors have declared no conflicts of interest.