HER1-ECD vaccination dispenses with emulsification to elicit HER1-specific anti-proliferative effects.

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.

Hapten-mediated recruitment of polyclonal antibodies to tumors engenders antitumor immunity.

Uptake of tumor antigens by tumor-infiltrating dendritic cells is limiting step in the induction of tumor immunity, which can be mediated through Fc receptor (FcR) triggering by antibody-coated tumor cells. Here we describe an approach to potentiate tumor immunity whereby hapten-specific polyclonal antibodies are recruited to tumors by coating tumor cells with the hapten. Vaccination of mice against dinitrophenol (DNP) followed by systemic administration of DNP targeted to tumors by conjugation to a VEGF or osteopontin aptamer elicits potent FcR dependent, T cell mediated, antitumor immunity. Recruitment of αGal-specific antibodies, the most abundant naturally occurring antibodies in human serum, inhibits tumor growth in mice treated with a VEGF aptamer-αGal hapten conjugate, and recruits antibodies from human serum to human tumor biopsies of distinct origin. Thus, treatment with αGal hapten conjugated to broad-spectrum tumor targeting ligands could enhance the susceptibility of a broad range of tumors to immune elimination.

Anti-EGFR activation, anti-proliferative and pro-apoptotic effects of polyclonal antibodies induced by EGFR-based cancer vaccine.

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.