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.
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 (Ab2beta) 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.
Coelho
M
M
Tumour Immunotargeting and Antibody Engineering, INSERM, EMI0227, 34298 Montpellier, France.
Gauthier
P
P
Pugnière
M
M
Roquet
F
F
Pèlegrin
A
A
Navarro-Teulon
I
I
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000276:immunology*; D016466:CHO Cells; D019496:Cancer Vaccines; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology; D007167:Immunotherapy; D051379:Mice; D010051:Ovarian Neoplasms / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007128:Immunoglobulin Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases