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Antibodies 2015, 4(4), 426-440; doi:10.3390/antib4040426

Bispecific CD3/HER2 Targeting FynomAb Induces Redirected T Cell-Mediated Cytolysis with High Potency and Enhanced Tumor Selectivity

Covagen AG, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Wagistrasse 25, 8952 Schlieren, Switzerland
Current address: Grabulovski Consulting Services GmbH, Riedhofstrasse 57, 8049 Zurich, Switzerland.
§
I.Z. passed away between completion of the study and manuscript submission.
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Christian Klein
Received: 13 October 2015 / Revised: 30 November 2015 / Accepted: 1 December 2015 / Published: 8 December 2015
(This article belongs to the Special Issue Advances in Bispecific Antibodies)
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Abstract

CD3 bispecific therapies retargeting T cells to tumors have recently demonstrated striking activity in patients. Several CD3 bispecific antibodies directed against various tumor targets are currently being investigated in the clinic across different tumors. One limitation of these therapies is the risk of target-related toxicity due to low-level expression of tumor antigen in normal tissue. In this study we have engineered a bispecific CD3/HER2 FynomAb, COVA420, which redirects T cells with high potency and selectivity to tumor cells with high HER2 expression in vitro and in vivo. COVA420 activity depends on high HER2 density as no activity was observed on cells with lower HER2 levels as found in human normal tissue. These results suggest that COVA420 may spare normal tissue expressing low levels of HER2 while still having uncompromised efficacy on tumor cells with high HER2 expression. This concept may be applied to other cancer antigens that otherwise cannot be targeted by T cell redirecting approaches, and may therefore expand the applicability of CD3 bispecific FynomAbs to a larger number of solid tumors. View Full-Text
Keywords: FynomAb; Fynomer; bispecific antibody; T cell retargeting; oncology; CD3; HER2; selectivity; toxicity FynomAb; Fynomer; bispecific antibody; T cell retargeting; oncology; CD3; HER2; selectivity; toxicity
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MDPI and ACS Style

Wuellner, U.; Klupsch, K.; Buller, F.; Attinger-Toller, I.; Santimaria, R.; Zbinden, I.; Henne, P.; Grabulovski, D.; Bertschinger, J.; Brack, S. Bispecific CD3/HER2 Targeting FynomAb Induces Redirected T Cell-Mediated Cytolysis with High Potency and Enhanced Tumor Selectivity. Antibodies 2015, 4, 426-440.

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