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Pharmacokinetics, biodistribution and biological effects of intravenously administered bispecific monoclonal antibody OC/TR F(ab′) 2 in ovarian carcinoma patients
Author(s) -
Tibben Jacoba G.,
Boerman Otto C.,
Massuger Leon F. A. G.,
Schijf Charles P. T.,
Claessens Roland A. M. J.,
Corstens Frans H. M.
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960516)66:4<477::aid-ijc11>3.0.co;2-5
Subject(s) - monoclonal antibody , ovarian cancer , medicine , pharmacokinetics , ovarian carcinoma , antibody , cytolysis , toxicity , biodistribution , pharmacology , cancer , immunology , cytotoxicity , chemistry , in vivo , biology , in vitro , biochemistry , microbiology and biotechnology
The bispecific monoclonal antibody (biMAb) OC/TR combines the anti‐ovarian‐cancer reactivity of the MOv18 monoclonal antibody (MAb) with the reactivity of an anti‐CD3 MAb. Pre‐clinical studies have indicated that this biMAb is able to redirect the cytolytic activity of T cells towards tumour cells, resulting in efficient tumour‐cell lysis. To assess the clinical potential of systemic biMAb‐based cancer therapy we initiated a study in ovarian‐cancer patients. Five patients suspected of ovarian cancer received 123 I‐OC/TR F(ab′) 2 i.v. Unexpectedly, the first patient developed side effects (grade III–IV toxicity) starting 30 min after infusion (p.i.) of 1 mg of OC/TR F(ab′) 2 . After approval of the Ethical Committee, the study was continued at lower dose levels (0.1 mg; 0.2 mg). However, at the 0.2‐mg dose level similar side effects were observed. FACS analysis indicated that all peripheral T cells were coated with biMAb immediately following the infusion. The cytokines tumour necrosis factor‐α, interferon‐γ and interleukin‐2 showed maximum serum concentrations 2 h p.i. Tumour uptake ranged from 0.8 to 1.9% ID/kg, resulting in tumour/background ratios of 3 to 8. Our results suggest that at higher antibody dose levels OC/TR F(ab′) 2 causes T‐cell activation with acute release of cytokines. Only low doses of biMAb can be administered safely. Despite the interaction with T cells, OC/TR F(ab′) 2 preferentially localizes in tumours following i.v. administration, thus offering therapeutic perspectives. © 1996 Wiley‐Liss, Inc.