ABSTRACT
EGFR (HER1) highlights as one of the most relevant tumor associated antigen in epithelial malignant cells. Monoclonal antibodies and tyrosine kinase inhibitors against EGFR remain as the most advanced approaches in clinical trials. More recently, an active immunotherapy using the HER1 extracellular domain (ECD) adjuvated in very small size proteoliposomes (VSSP) and emulsified in Montanide ISA-51 demonstrated its strength to inhibit tumor cell line proliferation by arresting cells in G(0)/G(1) stage and induction of apoptosis. In this study, we present a simpler HER1-ECD-based formulation, which is lacking the oily component Montanide ISA-51. Generated antibodies following non-emulsive formulation immunization recognized membrane EGFR; avoid EGF and TGFalpha coupling to EGFR leading to a marked abrogation of EGFR phosphorylation levels. Non-emulsive formulation also arrests cell cycle in G(0)/G(1) stage, demonstrating it preserves previous formulation quality in a newer and simpler formulation.
Subject(s)
Adjuvants, Immunologic/pharmacology , Cancer Vaccines/immunology , ErbB Receptors/immunology , Liposomes/pharmacology , Animals , Antibodies, Neoplasm/blood , Cell Line , Female , Humans , Immunization, Secondary/methods , Mice , Mice, Inbred BALB C , Mice, Inbred C57BLABSTRACT
Up to now clinical experiences focusing EGF receptor, an attractive target for cancer therapy, have been limited to passive therapies, suggesting that therapeutic cancer vaccines inducing anti-epidermal growth factor receptor (EGFR) antibodies could also work. Here, the humoral immune response induced in mice with a vaccine formulation containing the human EGFR-extracellular domain and very small-sized proteoliposomes (VSSP), a novel nanoparticulated adjuvant was assessed. In vaccinated mice sera average of the specific polyclonal antibodies (PAb) titers was 10(-5). Anti-EGFR PAb were able to bind EGFR+ tumor cell lines, expressing different levels of the molecule. Noteworthy, the presence of Cetuximab only partially inhibited the vaccine-induced antibodies binding to H125 cells. Anti-EGFR PAb abrogated ligands-dependent EGFR phosphorylation, provoking tumor cells apoptosis. The described EGFR-based vaccine might be a superior therapeutic approach for patients with EGFR+ tumors.