title: Humoral anti-OV-TL 3 response after the intravenous administration of radiolabelled Fab' or F(ab')2 fragments in ovarian cancer patients.
abstract: The human anti-mouse antibody (HAMA) response was determined in the serum of patients suspected of having ovarian cancer who underwent radioimmunoscintigraphy with either 99Tcm-OV-TL 3 Fab' (n = 20) or 111In-DTPA-OV-TL 3 F(ab')2 (n = 73). Blood samples were collected prior to and at several time points post-intravenous injection. The detection of HAMA was performed with an in-house OV-TL 3 F(ab')2-based sandwich-type immunoradiometric assay (IRMA). The homologous IRMA demonstrated that 8 of 20 (40%) patients had developed HAMA responses after injection of Fab' fragments and that 14 of 73 (19%) patients had developed HAMA responses after F(ab')2 administration. The subclass of the measured HAMA was analysed in a limited number of samples, showing IgG or IgM as well as mixed responses. The kinetics of the HAMA responses varied greatly. Our study showed the relevance of the sampling time and frequency: HAMA responses can be easily underestimated with a low sampling frequency. The homologous IRMA described in this study was able to quantify the OV-TL 3-specific HAMA responses. With additional assays, the subclass of the HAMA could be further analysed. Remarkably, the fraction of HAMA responders after injection of OV-TL 3 Fab' fragments was in the same range as the proportion of HAMA responders after F(ab')2 administration.
authors.affiliation: Department of Obstetrics and Gynaecology, University Hospital Nijmegen St Radboud, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: Tibben
authors.forename: C M
authors.initials: CM
authors.lastname: Thomas
authors.forename: L F
authors.initials: LF
authors.lastname: Massuger
authors.forename: M F
authors.initials: MF
authors.lastname: Segers
authors.forename: C P
authors.initials: CP
authors.lastname: Schijf
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000276:immunology; D002614:Chelating Agents; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D015592:Immunoradiometric Assay; D007205:Indium Radioisotopes; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology*; D004369:Pentetic Acid; D016719:Radioimmunodetection; D013045:Species Specificity
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D002614:Chelating Agents; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007205:Indium Radioisotopes; D004369:Pentetic Acid