Bispecific CD3/HER2 Targeting FynomAb Induces Redirected T Cell-Mediated Cytolysis with High Potency and Enhanced Tumor Selectivity
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- Ulrich Wuellner
- Covagen AG, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Wagistrasse 25, 8952 Schlieren, Switzerland
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- Kristina Klupsch
- Covagen AG, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Wagistrasse 25, 8952 Schlieren, Switzerland
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- Fabian Buller
- Covagen AG, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Wagistrasse 25, 8952 Schlieren, Switzerland
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- Isabella Attinger-Toller
- Covagen AG, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Wagistrasse 25, 8952 Schlieren, Switzerland
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- Roger Santimaria
- Covagen AG, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Wagistrasse 25, 8952 Schlieren, Switzerland
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- Irene Zbinden
- Covagen AG, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Wagistrasse 25, 8952 Schlieren, Switzerland
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- Patricia Henne
- Covagen AG, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Wagistrasse 25, 8952 Schlieren, Switzerland
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- Dragan Grabulovski
- Covagen AG, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Wagistrasse 25, 8952 Schlieren, Switzerland
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- Julian Bertschinger
- Covagen AG, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Wagistrasse 25, 8952 Schlieren, Switzerland
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- Simon Brack
- Covagen AG, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, Wagistrasse 25, 8952 Schlieren, Switzerland
説明
<jats:p>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.</jats:p>
収録刊行物
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- Antibodies
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Antibodies 4 (4), 426-440, 2015-12-08
MDPI AG