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

被引:6
作者
Aguiar Alpizar, Yeranddy [1 ]
Sanchez Ramirez, Belinda [1 ]
Hernandez Fernadez, Diana Rosa [1 ]
Rabasa Capote, Ailem [1 ]
Garrido Hidalgo, Greta [1 ]
Perez Rodriguez, Rolando [2 ]
Fernandez Molina, Luis Enrique [1 ]
机构
[1] Ctr Mol Immunol, Vaccine Dept, Havana 16040, Cuba
[2] Ctr Mol Immunol, Res & Dev Direct, Havana 16040, Cuba
来源
HUMAN VACCINES | 2009年 / 5卷 / 03期
关键词
EGFR; active immunotherapy; HER1; vaccine; non-emulsive formulation; cell cycle arrest; cancer vaccine; EPIDERMAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; FACTOR RECEPTOR; CANCER VACCINE; CARCINOMA-CELLS; ERBB RECEPTORS; BREAST-CANCER; ACTIVATION; IMMUNOTHERAPY; ADJUVANT;
D O I
10.4161/hv.5.3.7129
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 TGF alpha 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.
引用
收藏
页码:158 / 165
页数:8
相关论文
共 30 条
[21]   Immunogene therapy of tumors with vaccine based on xenogeneic epidermal growth factor receptor [J].
Lu, Y ;
Wei, YQ ;
Tian, L ;
Zhao, X ;
Yang, L ;
Hu, B ;
Kan, B ;
Wen, YJ ;
Liu, F ;
Deng, HX ;
Li, JO ;
Mao, YQ ;
Lei, S ;
Huang, MJ ;
Peng, F ;
Jiang, Y ;
Zhou, H ;
Zhou, LQ ;
Luo, F .
JOURNAL OF IMMUNOLOGY, 2003, 170 (06) :3162-3170
[22]   Challenges facing adjuvants for cancer immunotherapy [J].
Mesa, C ;
Fernández, LE .
IMMUNOLOGY AND CELL BIOLOGY, 2004, 82 (06) :644-650
[23]   Very small size proteoliposomes derived from Neisseria meningitidis:: an effective adjuvant for Th1 induction and dendritic cell activation [J].
Mesa, C ;
de León, J ;
Rigley, K ;
Fernández, LE .
VACCINE, 2004, 22 (23-24) :3045-3052
[24]  
Pal SK, 2005, ANTI-CANCER DRUG, V16, P483
[25]   Active antimetastatic immunotherapy in Lewis lung carcinoma with self EGFR extracellular domain protein in VSSP adjuvant [J].
Ramirez, Belinda Sanchez ;
Pestana, Eduardo Suarez ;
Hidalgo, Greta Garrido ;
Garcia, Tays Hernandez ;
Rodriguez, Rolando Perez ;
Ullrich, Axel ;
Fernandez, Luis Enrique .
INTERNATIONAL JOURNAL OF CANCER, 2006, 119 (09) :2190-2199
[26]   Blockade of epidermal growth factor receptors chemosensitizes breast cancer cells through up-regulation of Bnip3L [J].
Real, PJ ;
Benito, A ;
Cuevas, J ;
Berciano, MT ;
de Juan, A ;
Coffer, P ;
Gomez-Roman, J ;
Lafarga, M ;
Lopez-Vega, JM ;
Fernandez-Luna, JL .
CANCER RESEARCH, 2005, 65 (18) :8151-8157
[27]   Anti-EGFR activation, anti-proliferative and pro-apoptotic effects of polyclonal antibodies induced by EGFR-based cancer vaccine [J].
Sanchez Ramirez, Belinda ;
Aguiar Alpizar, Yeranddy ;
Hernandez Fernandez, Diana Rosa ;
Garrido Hidalgo, Greta ;
Rabasa Capote, Ailem ;
Perez Rodriguez, Rolando ;
Enrique Fernandez, Luis .
VACCINE, 2008, 26 (38) :4918-4926
[28]  
Tüting T, 1998, J IMMUNOL, V160, P1139
[29]   TUMOR-ANTIGENS [J].
URBAN, JL ;
SCHREIBER, H .
ANNUAL REVIEW OF IMMUNOLOGY, 1992, 10 :617-644
[30]   EGFR tyrosine kinase inhibitor AG1478 inhibits cell proliferation and arrests cell cycle in nasopharyngeal carcinoma cells [J].
Zhu, XF ;
Liu, ZC ;
Xie, BF ;
Li, ZM ;
Feng, GK ;
Yang, DJ ;
Zeng, YX .
CANCER LETTERS, 2001, 169 (01) :27-32