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British Journal of Cancer (2004) 90, 2032-2041.
doi:10.1038/sj.bjc.6601825 Published online 27 April 2004
Isolation and characterisation of a human anti-idiotypic scFv used as a surrogate tumour antigen to elicit an anti-HER-2/neu humoral response in mice
M Coelho1, P Gauthier1, M Pugnière2, F Roquet2, A Pèlegrin1 and I Navarro-Teulon1
1Tumour Immunotargeting and Antibody Engineering, INSERM, EMI0227, 34298 Montpellier, France
2Center for Pharmacology and Health Biotechnology, CNRS, UMR 5160, 34093 Montpellier, France
Correspondence to: Dr I Navarro-Teulon, Centre de Recherche en Cancérologie, CRLC Val d'Aurelle-Paul Lamarque, Parc Euromédecine, 34298 Montpellier Cedex 5, France. E-mail: iteulon@valdorel.fnclcc.fr
Received 16 January 2004; accepted 8 March 2004; published online 27 April 2004
HER-2/neu is a tumour antigen that is overexpressed in human breast tumours. Among the vaccine strategies developed to overcome immune tolerance to self-proteins, vaccination with anti-idiotypic (anti-Id) antibodies has been described as a promising approach for treatment of several malignant diseases. To develop an active immunotherapy for cancer patients positive for HER-2/neu, we investigated immunisation with human anti-Id single-chain fragments (scFv) mimicking the conformation of HER-2/neu protein to induce a humoral response in mice. We selected by phage display two human anti-Id scFv (Ab2
) directed against trastuzumab F(ab')2 fragments (Ab1), a humanised anti-HER-2/neu monoclonal antibody. Using competitive ELISA and Biacore biosensor analysis, we showed that anti-Id scFv 40 and scFv 69 could inhibit HER-2/neu binding to trastuzumab. Following vaccination of BALB/c mice with the soluble or phage-displayed scFv, Ab3 polyclonal antibodies, and among them Ab1' antibodies able to bind HER-2/neu, were detected in the sera of the immunised mice. These results demonstrate that the human anti-Id scFv could act as a surrogate antigen for HER-2/neu. The present study strongly suggests that the novel 30 kDa human mini-antibody could be used as an anti-idiotype-based vaccine formulation to induce an effective humoral response in patients bearing HER-2/neu-positive tumours.Keywords: anti-idiotypic antibody; HER-2/neu; vaccine; active immunotherapy
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| Print ISSN: 0007-0920 | Online ISSN: 1532-1827 | © 2004 Cancer Research UK | ||
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