Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody
Ralf Bargou,1,2*
Eugen Leo,3*
Gerhard Zugmaier,3
Matthias Klinger,3
Mariele Goebeler,1,2
Stefan Knop,2
Richard Noppeney,4
Andreas Viardot,5
Georg Hess,6
Martin Schuler,7
Hermann Einsele,2
Christian Brandl,3
Andreas Wolf,3
Petra Kirchinger,3
Petra Klappers,3
Margit Schmidt,3
Gert Riethmüller,8
Carsten Reinhardt,3
Patrick A. Baeuerle,3
Peter Kufer3
Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non–Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell–engaging antibodies appear to have therapeutic potential for the treatment of malignant diseases.
1 Interdisciplinary Phase I/II Unit of the University of Würzburg, Klinikstraße 6-8, 97070 Würzburg, Germany.
2 Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Klinikstraße 6-8, 97070 Würzburg, Germany.
3 Micromet AG, Staffelseestraße 2, 81477 Munich, Germany; and Micromet, Incorporated, 6707 Democracy Boulevard, Bethesda, MD 20817, USA.
4 Universitätsklinikum Essen, Klinik für Hämatologie, Medizinische Klinik und Poliklinik, Hufelandstraße 55, 45147 Essen, Germany.
5 Universitätsklinikum Ulm, Innere Medizin III, Robert-Koch-Straße 8, 89081 Ulm, Germany.
6 Klinikum der Johannes-Gutenberg Universität III, Medizinische Klinik und Poliklinik, Langenbeckstraße 1, 55131 Mainz, Germany.
7 Universitätsklinikum Essen, Innere Klinik (Tumorforschung), Tumorforschung, Hufelandstraße 55, 45122 Essen, Germany.
8 Institute for Immunology, Ludwig-Maximilians-Universität, Goethestraße 31, 81333 Munich, Germany.
* These authors contributed equally to this work.
Present address: Johnson and Johnson Pharmaceuticals, Turnhoutsebaan 30, 2340 Beerse, Belgium.
To whom correspondence should be addressed. E-mail: patrick.baeuerle{at}micromet-inc.com
