Targeting properties of an anti-CD16/anti-CD30 bispecific: antibody in an in vivo system

Bispecific antibodies are currently being used in clinical trials in increa sing 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 bispe cific anti body and demonstrated a 30% response rate in a cohort of patient s otherwise resistant to standard therapeutic modalities. However, no surro gate marker could be defined in these trials indicative of optimal antibody dosing/scheduling or predictive for favorable response. In order to evalua te accurately the potential biodistribution properties of bispecific antibo dy in patients, we have performed a detailed analysis of the binding proper ties and animal model in vivo characteristics of these constructs. For this purpose, the parental antibodies (anti-CD30 and anti-CD16) and the bispeci fic antibody (anti-CD30/anti-CD16) were radiolabeled with either I-125 or I n-111. Antibody integrity and binding properties after labeling were confir med by Scatchard plot and Lindmo analysis. In-111-labeled antibodies reveal ed superior targeting properties in a standard SCID mouse tumor model. Both the bivalent parental anti-CD30 monoclonal antibody and the monovalent ant i-CD30/ anti-CD16 bispecific antibody showed excellent uptake in CD30(+) tu mors 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 t argeting properties of the bispecific antibody compared with the parental a nti-CD30 antibody encourages the further clinical development of this bispe cific antibody, and might help to explain the clinical responses seen with this antibody so far in patients suffering from Hodgkin's disease.