CIMAvax-EGF: A New Therapeutic Vaccine for Advanced Non-Small Cell Lung Cancer Patients

Abstract

Lung cancer is the common fatal illness with the highest incidence and mortality globally. Epidermal growth factor receptor overexpression by tumor cells is associated with uncontrolled proliferation, angiogenesis, anti-apoptotic signals, metastization, and invasiveness. CIMAvax-EGF vaccine consists of a chemical conjugate of the EGF with the P64 protein derived from the Meningitis B bacteria and Montanide ISA 51, as adjuvant. The vaccine is projected to induce antibodies against EGF that results in EGF withdrawal. CIMAvax-EGF demonstrated to be safe and immunogenic in advanced non-small cell lung cancer (NSCLC) patients. The efficacy study was an open-label, multicentric Phase III clinical trial, which enrolled 405 advanced NSCLC patients. Patients with proven stage IIIB/IV NSCLC, who had completed four to six cycles of chemotherapy (CTP) were randomized to receive CIMAvax-EGF or best supportive care. CIMAvax-EGF resulted in a significantly larger overall survival in patients receiving at least four doses. High EGF concentration at baseline was a good predictive biomarker of the vaccine activity and a poor prognostic biomarker for the non-treated population. The proportion of CD8+CD28− cells, CD4 cells, and the CD4/CD8 ratio after first-line CTP was also associated with CIMAvax-EGF clinical benefit. After completing the Phase III, a Phase IV trial was done where the vaccine was administered in primary care units. Administering the vaccine at primary care institutions granted better access and treatment compliance. Safety was confirmed. Several clinical trials are currently ongoing to validate EGF as a predictive biomarker of CIMAvax-EGF efficacy.

Overexpression of CXCR4 promotes invasion and migration of non‑small cell lung cancer via EGFR and MMP‑9

“…Of the lung cancer cases diagnosed, ~85% are non-small cell lung cancer (NSCLC), which has a poor prognosis and is difficult to treat (2). Despite years of research (3,4), the survival rate of patients with NSCLC remains poor. Therefore, understanding the pathogenesis of lung cancer is important to those patients with NSCLC.…”

Anti-EGF antibodies as surrogate biomarkers of clinical efficacy in stage IIIB/IV non-small-cell lung cancer patients treated with an optimized CIMAvax-EGF vaccination schedule

“…This behavior is in line with some experimental evidences showing that the immunodominant nature of an antigenic determinant is not affected by its concentration, position within the sequence of a given protein or the route of administration. 32 Although it is well known that the administration of CIMAvax-EGF using different immunization schemes was able to induce an IgG response, 29 there is not a detailed report about the subclass distribution during patient's immunization. In agreement with previous data, 14 an IgG3 Ab response was generated after 3 months of vaccination, which is associated with the immune response against proteins and the secretion of Th1 cytokines.…”

Active immunotherapy of cancer: An overview of therapeutic vaccines

“…Gen koji kodira EGF receptor (EGFR) je dobro poznat onkogen. Pojačana aktivacija ovog gena može dovesti do maligne transformacije normalne ćelije, uzrokujući ćelijsku proliferaciju, inhibiciju apoptoze, angiogenezu i tumorom indukovane proinflamatorne i imunosupresivne procese (54). Generisanje signala posredstvom EGFR može biti smanjeno snižavanjem nivoa EGF ili direktnom blokadom receptora primenom specifičnih monoklonskih antitela.…”

“…Snižavanje nivoa EGF aktivnom imunoterapijom je koncept koji su razvili kubanski istraživači. Vakcina stimuliše imunski sistem pacijenta da sintetiše i sekretuje sopstvena efektorska anti-EGF antitela koja vezuju i neutrališu EGF, što posledično dovodi do smanjivanja veličine tumora ili sprečava njegov dalji razvoj (54,55,56).…”