caa a22 4500 47713808X CHVBK 20180405111724.0 cr unu---uuuuu 170330e19971201xx s 000 0 eng 10.1023/A:1008848905210 doi (NATIONALLICENCE)springer-10.1023/A:1008848905210 Pretargeted radioimmunotherapy using 131I-labelled bivalent hapten-bearing peptides [Elektronische Daten] [Marc de Boisferon, Corrine Manetti, Olivier Raguin, Emmanuel Gautherot, William Rostène, Jacques Barbet, Anne Gruaz-Guyon] The advantages of bivalent hapten-bearing peptides for the detection oftumours pretargeted with bispecific antibodies have been demonstrated. Thistechnology is now considered for radioimmunotherapy and bivalent haptensdesigned to target 131I are needed. We thus synthesised aseries of tyrosine-containing peptides bearing the histamine-hemisuccinatehapten. These molecules were tested for their ability to bind simultaneouslytwo anti-hapten antibody molecules. One of these bivalent haptens, AG3.0,with a lysyl-d-tyrosyl-lysine connecting chain, was found to have optimalbinding characteristics and was thus selected for further investigations.AG3.0 was shown to efficiently deliver radioactive iodine to humancolorectal tumours grafted in nude mice using an anti-carcinoembryonicantigen×anti-histamine-hemisuccinate bispecific antibody. AG3.0 wasalso targeted to human B lymphoma cells pretargeted with a bispecificantibody specific for membrane IgM. In this system, bivalent ligands such asF(ab′)2 or IgG are rapidly internalised and covalentlylinked radioactive iodine is released from target cells as a result ofintracellular catabolism. With the pretargeted iodine-labelled bivalenthapten, a fivefold increase in the intracellular activity retention time ascompared to 125I-labelled F(ab′)2 and IgGwas observed. The radiolabelled hapten did not undergo any degradation afterinternalisation. These results have been confirmed in vivo with ananti-BCL1 IgM idiotype bispecific antibody and131I-labelled AG3.0. These reagents injected as a single 300µCi dose, 7 days after inoculation of 104BCL1 lymphoma cells in BALB/c mice, cured 14/16 of the animalsand the treatment was well tolerated. Comparatively, the same dose oflabelled IgG cured 13/16 of the mice but three mice died of haematologictoxicity. The same dose of labelled F(ab′)2 orFab′ was completely inefficient. was completely inefficient. 131I-labelled bivalenthaptens are now used in phase I radioimmunotherapy clinical trials. Kluwer Academic Publishers, 1997 Carcinoembryonic antigen nationallicence Colon cancer nationallicence Lymphoma nationallicence Monoclonal antibodies nationallicence Targeting nationallicence de Boisferon Marc Inserm U339, Hôpital and Faculté de Médecine Saint Antoine, 27 Rue Chaligny, F-75012, Paris, France aut Manetti Corrine Immunotech S.A., 130 Avenue de Lattre de Tassigny, BP176 F-13276, Marseille Cedex 9, France aut Raguin Olivier Inserm U339, Hôpital and Faculté de Médecine Saint Antoine, 27 Rue Chaligny, F-75012, Paris, France aut Gautherot Emmanuel Immunotech S.A., 130 Avenue de Lattre de Tassigny, BP176 F-13276, Marseille Cedex 9, France aut Rostène William Inserm U339, Hôpital and Faculté de Médecine Saint Antoine, 27 Rue Chaligny, F-75012, Paris, France aut Barbet Jacques Immunotech S.A., 130 Avenue de Lattre de Tassigny, BP176 F-13276, Marseille Cedex 9, France aut Gruaz-Guyon Anne Inserm U339, Hôpital and Faculté de Médecine Saint Antoine, 27 Rue Chaligny, F-75012, Paris, France aut Letters in Peptide Science Kluwer Academic Publishers 4/4-6(1997-12-01), 331-339 0929-5666 4:4-6<331 1997 4 10989 https://doi.org/10.1023/A:1008848905210 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1008848905210 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- de Boisferon Marc Inserm U339, Hôpital and Faculté de Médecine Saint Antoine, 27 Rue Chaligny, F-75012, Paris, France aut NATIONALLICENCE 700 1- Manetti Corrine Immunotech S.A., 130 Avenue de Lattre de Tassigny, BP176 F-13276, Marseille Cedex 9, France aut NATIONALLICENCE 700 1- Raguin Olivier Inserm U339, Hôpital and Faculté de Médecine Saint Antoine, 27 Rue Chaligny, F-75012, Paris, France aut NATIONALLICENCE 700 1- Gautherot Emmanuel Immunotech S.A., 130 Avenue de Lattre de Tassigny, BP176 F-13276, Marseille Cedex 9, France aut NATIONALLICENCE 700 1- Rostène William Inserm U339, Hôpital and Faculté de Médecine Saint Antoine, 27 Rue Chaligny, F-75012, Paris, France aut NATIONALLICENCE 700 1- Barbet Jacques Immunotech S.A., 130 Avenue de Lattre de Tassigny, BP176 F-13276, Marseille Cedex 9, France aut NATIONALLICENCE 700 1- Gruaz-Guyon Anne Inserm U339, Hôpital and Faculté de Médecine Saint Antoine, 27 Rue Chaligny, F-75012, Paris, France aut NATIONALLICENCE 773 0- Letters in Peptide Science Kluwer Academic Publishers 4/4-6(1997-12-01), 331-339 0929-5666 4:4-6<331 1997 4 10989 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer