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.
Ramírez
Belinda Sánchez
BS
Vaccine Department, Center of Molecular Immunology, Atabey-Siboney, Playa, Havana, Cuba. belinda@cim.sld.cu
Alpízar
Yeranddy Aguiar
YA
Fernández
Diana Rosa Hernández
DR
Hidalgo
Greta Garrido
GG
Capote
Ailem Rabasa
AR
Rodríguez
Rolando Pérez
RP
Fernández
Luis Enrique
LE
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects; D017209:Apoptosis / Q000276:immunology*; D018938:Caco-2 Cells; D019496:Cancer Vaccines / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000276:immunology; D011510:Proteolipids; D016211:Transforming Growth Factor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000906:Antibodies; D019496:Cancer Vaccines; D011510:Proteolipids; D016211:Transforming Growth Factor alpha; C020485:proteoliposomes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors