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

被引:23
作者
Sanchez Ramirez, Belinda [1 ]
Aguiar Alpizar, Yeranddy [1 ]
Hernandez Fernandez, Diana Rosa [1 ]
Garrido Hidalgo, Greta [1 ]
Rabasa Capote, Ailem [1 ]
Perez Rodriguez, Rolando [2 ]
Enrique Fernandez, Luis [1 ]
机构
[1] Ctr Mol Immunol, Vaccine Dept, Havana 11600, Cuba
[2] Ctr Mol Immunol, Res & Dev Direct, Havana 11600, Cuba
关键词
vaccine; cancer; polyclonal antibodies;
D O I
10.1016/j.vaccine.2008.07.018
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4918 / 4926
页数:9
相关论文
共 51 条
[1]  
BERGH J, 1985, ACTA PATH MICRO IM A, V93, P133
[2]   Ligand-independent oncogenic signaling by the epidermal growth factor receptor: v-ErbB as a paradigm [J].
Boerner, JL ;
Danielsen, A ;
Maihle, NJ .
EXPERIMENTAL CELL RESEARCH, 2003, 284 (01) :111-121
[3]   Supra-additive cytotoxic effects of a combination of cytostatic drugs and antibody-induced complement activation on tumor cells in vitro [J].
Brezicka, T ;
Einbeigi, Z .
TUMOR BIOLOGY, 2001, 22 (02) :97-103
[4]  
CARNEY DN, 1985, CANCER RES, V45, P2913
[5]   Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients [J].
Crombet, T ;
Osorio, M ;
Cruz, T ;
Roca, C ;
del Castillo, R ;
Mon, R ;
Iznaga-Escobar, N ;
Figueredo, R ;
Koropatnick, J ;
Renginfo, E ;
Fernández, E ;
Alvárez, D ;
Torres, O ;
Ramos, M ;
Leonard, I ;
Pérez, R ;
Lage, A .
JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (09) :1646-1654
[6]   EXPRESSION OF EPIDERMAL GROWTH-FACTOR RECEPTOR AND SURVIVAL IN UPPER AERODIGESTIVE TRACT CANCER [J].
DASSONVILLE, O ;
FORMENTO, JL ;
FRANCOUAL, M ;
RAMAIOLI, A ;
SANTINI, J ;
SCHNEIDER, M ;
DEMARD, F ;
MILANO, G .
JOURNAL OF CLINICAL ONCOLOGY, 1993, 11 (10) :1873-1878
[7]   Enhancement of the immune response to poorly immunogenic gangliosides after incorporation into very small size proteoliposomes (VSSP) [J].
Estevez, F ;
Carr, A ;
Solorzano, L ;
Valiente, O ;
Mesa, C ;
Barroso, O ;
Sierra, GV ;
Fernandez, LE .
VACCINE, 1999, 18 (1-2) :190-197
[8]  
FEN H, 2002, BLOOD, V100, P4108
[9]   Induction of T(H)1 and T(H)2 immunity in neonatal mice [J].
Forsthuber, T ;
Yip, HC ;
Lehmann, PV .
SCIENCE, 1996, 271 (5256) :1728-1730
[10]   The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors [J].
Garrett, TPJ ;
McKern, NM ;
Lou, MZ ;
Elleman, TC ;
Adams, TE ;
Lovrecz, GO ;
Kofler, M ;
Jorissen, RN ;
Nice, EC ;
Burgess, AW ;
Ward, CW .
MOLECULAR CELL, 2003, 11 (02) :495-505