HER1-ECD vaccination dispenses with emulsification to elicit HER1-specific anti-proliferative effects
Yeranddy Aguiar Alpízar1, Belinda Sánchez Ramírez, Diana Rosa Hernández Fernández
1Vaccine Department, Centre for Molecular Immunolgy, Habana, Cuba.
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.
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.
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