Abstract 2368: Inhibition of epidermal growth factor receptor pathway by epidermal growth factor antibodies in non-small cell lung cancer

Abstract

Abstract Introduction: The Epidermal Growth Factor Receptor (EGFR) signaling system is frequently unbalanced in non-small-cell lung cancer (NSCLC). Epidermal Growth Factor (EGF) could be an attractive target in these tumors. We used a “cancer vaccine” composed of human recombinant EGF conjugated to a carrier protein P64K. The vaccine is intended to induce antibodies against patients’ own EGF that would block EGF-EGFR interaction. Objectives: In NSCLC cell lines we assessed whether anti-EGF antibodies can inhibit the pathway activated by EGF-EGFR binding and whether sera from immunized patients can block downstream key signal transduction proteins. NSCLC cell lines were selected to determine whethergenetic alterations in EGFR, KRAS, ALK, BRAF or MET can have an impact on inhibition of EGFR pathway by anti-EGF antibodies. Experimental Procedures: Western blotting was used to evaluate the capacity of antibodies and sera from patients to inhibit EGFR activation pathway. MTT assays were performed to evaluate the effects on tumor cell proliferation. Results: The anti-EGF antibodies showed a dose-dependent inhibitory effect on EGF-induced activation of EGFR and downstream pathway molecules such as Akt and ERK 1/2. This inhibition was observed in all cell lines tested, including KRAS, EGFR and BRAF mutated cells as well as cells with ALK translocations or MET amplification. Sera from 10 patients immunized with the P64K-EGF vaccine were then tested. All sera reversed EGF-induced activation of EGFR and ERK 1/2, but some sera were significantly more potent than others. By contrast, two control sera from non-vaccinated patients failed to inhibit EGF-induced phosphorylation of EGFR and ERK 1/2. Finally, anti-EGF antibodies were also able to block the stimulatory effects of EGF on the growth of some NSCLC cell lines. Conclusions: Anti EGF antibodies and sera from patients immunized with an “EGF vaccine”, called otherwise EGF Pathway Targeted Immunization inhibits EGFR signaling in NSCLC cell line models. This effect is independent of cells’ genetic background. Citation Format: Jordi Codony-Servat, Miguel Angel Molina-Vila, Jordi Bertran-Alamillo, Rafael Rosell, Erik D’Hondt. Inhibition of epidermal growth factor receptor pathway by epidermal growth factor antibodies in non-small cell lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2368.