PMID: 8581377Oct 1, 1995Paper

Bispecific monoclonal antibodies for intravenous treatment of carcinoma patients: immunobiologic aspects

Journal of Hematotherapy
B J KroesenL de Leij

Abstract

Immunobiologic parameters measured during a phase I trial of intravenously (i.v.) administered bispecific monoclonal antibodies (BsmAb) in renal cell carcinoma (RCC) patients are described. The BsmAb used, BIS-1, is reactive with a pancarcinoma-associated 38 kDa transmembrane glycoprotein, EGP-2, as well with the CD3 complex. Patients received during a 2 h i.v. infusion F(ab')2 fragments of BIS-1 at doses of 1, 3, or 5 micrograms/kg body weight during concomitantly applied subcutaneous (s.c.) IL-2 treatment. Acute but transient BIS-1 F(ab')2-related toxicity was observed at the 3 and 5 micrograms/kg dose level, and the maximum tolerated dose (MTD) was set at 5 micrograms/kg. A dose-dependent binding of BIS-1 F(ab')2 to circulating T lymphocytes was found. The in vivo occupancy of CD3 molecules on T lymphocytes was highest at teh end of the infusion period and then rapidly decreased, as shown by flow cytometry. A much slower decrease of BIS-1 F(ab')2 binding was observed in vitro, suggesting migration of BIS-1 F(ab')2-loaded T lymphocytes from the circulation. A strong but transitory leukopenia was observed, in which LFA-1 alpha bright, CD3/CD8 double positive T cells left the circulation preferentially. This phenomenon was most...Continue Reading

References

Jul 1, 1992·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·D T SleijferN H Mulder
Oct 1, 1991·European Journal of Immunology·G JungW Wilmanns
Jan 1, 1994·International Journal of Cancer. Supplement = Journal International Du Cancer. Supplement·L De LeijM J Mattes
Nov 1, 1993·Cancer Immunology, Immunotherapy : CII·B J KroesenT H The
Jan 1, 1993·Cancer Treatment and Research·M W FangerP M Guyre

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Citations

May 4, 2012·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Kirsten DettmarJudith Atz
Jun 6, 2000·Advanced Drug Delivery Reviews· de Leij LB J Kroesen
Sep 24, 2008·Expert Opinion on Investigational Drugs·Philipp Kiewe, Eckhard Thiel
Mar 17, 2001·International Journal of Cancer. Journal International Du Cancer·O ManzkeH Bohlen
Jul 10, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jos G W KosterinkLou F M H de Leij

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