Targeting properties of an anti-CD16/anti-CD30 bispecific antibody in an in vivo system |
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Authors: | Christoph Renner Ingo Stehle Fook Thean Lee Cathrine Hall Bruno Catimel Edouard C Nice Angela Mountain Angela Rigopoulos Martin W Brechbiel Michael Pfreundschuh Andrew M Scott |
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Institution: | (1) Medical Department I, Saarland University, Kirrberger Strasse, 66424 Homburg/Saar, Homburg, Germany Tel.: +49-6841-163002; Fax: +49-6841-163101, DE;(2) Ludwig Institute for Cancer Research, Austin & Repatriation Medical Center, Heidelberg, Victoria, Australia, AU;(3) Radioimmune and Inorganic Chemistry Section, ROB, DCS, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA, US |
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Abstract: | Bispecific antibodies are currently being used in clinical trials in increasing numbers in the areas of breast cancer, prostate
cancer, non-Hodgkin's lymphoma and Hodgkin's lymphoma. We have previously performed two clinical trials in patients with Hodgkin's
disease with an anti-CD30/anti-CD16 bispecific antibody and demonstrated a 30% response rate in a cohort of patients otherwise
resistant to standard therapeutic modalities. However, no surrogate marker could be defined in these trials indicative of
optimal antibody dosing/scheduling or predictive for favorable response. In order to evaluate accurately the potential biodistribution
properties of bispecific antibody in patients, we have performed a detailed analysis of the binding properties and animal
model in vivo characteristics of these constructs. For this purpose, the parental antibodies (anti-CD30 and anti-CD16) and
the bispecific antibody (anti-CD30/anti-CD16) were radiolabeled with either 125I or 111In. Antibody integrity and binding properties after labeling were confirmed by Scatchard plot and Lindmo analysis. 111In-labeled antibodies revealed superior targeting properties in a standard SCID mouse tumor model. Both the bivalent parental
anti-CD30 monoclonal antibody and the monovalent anti-CD30/anti-CD16 bispecific antibody showed excellent uptake in CD30+ tumors which did not differ significantly between the two (maximum uptake 16.5% ± 4.2% vs. 18.4% ± 3.8% injected dose/gram
tissue). The equivalent targeting properties of the bispecific antibody compared with the parental anti-CD30 antibody encourages
the further clinical development of this bispecific antibody, and might help to explain the clinical responses seen with this
antibody so far in patients suffering from Hodgkin's disease.
Received: 26 October 2000 / Accepted: 15 December 2000 |
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Keywords: | Bispecific antibodies Hodgkin's lymphoma Tumor targeting |
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