A llama single domain anti-idiotypic antibody mimicking HER2 as a vaccine: Immunogenicity and efficacy

被引:29
作者
Alvarez-Rueda, Nidia [1 ]
Ladjemi, Maha Zohra [1 ]
Behar, Ghislaine [2 ]
Corgnac, Stephanie [1 ]
Pugniere, Martine [3 ]
Roquet, Francoise [3 ]
Bascoul-Mollevi, Caroline [4 ]
Baty, Daniel [5 ]
Pelegrin, Andre [1 ]
Navarro-Teulon, Isabelle [1 ]
机构
[1] Univ Montpellier I, INSERM, U896, CRLC Val Aurelle Paul Lamarque,IRCM, F-34298 Montpellier 5, France
[2] CNRS, UMR 6204, Unite Biotechnol Biocatalyse & Bioregulat, F-44322 Nantes, France
[3] Ctr Etud Agents Pathogenes & Biotechnol Sante Pha, CNRS, UMR 5236, UM1,UM2, F-34093 Montpellier, France
[4] CRLC Val Aurelle Paul Lamarque, Unite Biostat, F-34298 Montpellier, France
[5] CNRS, UPR 9027, GDR 2352, Lab Ingn Syst Macromol, F-13402 Marseille, France
关键词
Llama antibodies; HER2; Anti-idiotypic vaccine; EPITHELIAL OVARIAN-CANCER; METASTATIC BREAST-CANCER; ANTITUMOR PROPERTIES; MONOCLONAL-ANTIBODY; HER-2/NEU; ANTIGEN; TRASTUZUMAB; PEPTIDE; PROTEIN; HERCEPTIN((R));
D O I
10.1016/j.vaccine.2009.05.067
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
HER2 over-expression in breast cancer correlates with reduced survival. Anti-idiotypic antibodies (Abs) that closely mimic HER2 could play a crucial role in the development of effective therapeutic vaccines. Here, we show that an anti-idiotypic single domain antibody (sdAb) 1HE isolated from a library generated from a Trastuzumab F(ab')(2)-immunized llama, closely mimics HER2. SdAb 1HE shows high affinity for Trastuzumab F(ab')(2), selectively inhibits HER2 binding to Trastuzumab F(ab')(2), and sera from sdAb 1HE-immunized BALB/c mice contain anti-HER2 antibodies that inhibit viability of HER2-positive cells. These results indicate that sdAb 1HE could be used as an anti-idiotype-based vaccine to boost immunity in patients bearing HER2-positive tumours. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4826 / 4833
页数:8
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