Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 15 August 2008:
Vol. 321. no. 5891, pp. 974 - 977
DOI: 10.1126/science.1158545
Prev | Table of Contents | Next

Reports

Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody

Ralf Bargou,1,2* Eugen Leo,3*{dagger} 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{ddagger} 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.

{dagger} Present address: Johnson and Johnson Pharmaceuticals, Turnhoutsebaan 30, 2340 Beerse, Belgium.

{ddagger} To whom correspondence should be addressed. E-mail: patrick.baeuerle{at}micromet-inc.com

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Investigational Immunotherapeutics for B-Cell Malignancies.
A. Quintas-Cardama, W. Wierda, and S. O'Brien (2010)
J. Clin. Oncol. 28, 884-892
   Abstract »    Full Text »    PDF »
Engineered Proteins Pull Double Duty.
J. R. Cochran (2010)
Science Translational Medicine 2, 17ps5
   Full Text »    PDF »
A Recombinant Bispecific Single-Chain Fragment Variable Specific for HLA Class II and Fc{alpha}RI (CD89) Recruits Polymorphonuclear Neutrophils for Efficient Lysis of Malignant B Lymphoid Cells.
Y. Guettinger, K. Barbin, M. Peipp, J. Bruenke, M. Dechant, H. Horner, D. Thierschmidt, T. Valerius, R. Repp, G. H. Fey, et al. (2010)
J. Immunol. 184, 1210-1217
   Abstract »    Full Text »    PDF »
Immunotherapy of Cancer: Key Findings and Commentary on the Third Tegernsee Conference.
D. Ruttinger, H. Winter, N. K. van den Engel, R. Hatz, K.-W. Jauch, B. A. Fox, and J. S. Weber (2010)
Oncologist 15, 112-118
   Abstract »    Full Text »    PDF »
Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for prime time?.
J. Delgado, D. W. Milligan, and P. Dreger (2009)
Blood 114, 2581-2588
   Abstract »    Full Text »    PDF »
Biodistribution of a Bispecific Single-chain Diabody and Its Half-life Extended Derivatives.
R. Stork, E. Campigna, B. Robert, D. Muller, and R. E. Kontermann (2009)
J. Biol. Chem. 284, 25612-25619
   Abstract »    Full Text »    PDF »
Bispecific T-Cell Engaging Antibodies for Cancer Therapy.
P. A. Baeuerle and C. Reinhardt (2009)
Cancer Res. 69, 4941-4944
   Abstract »    Full Text »    PDF »
The impact of Fc engineering on an anti-CD19 antibody: increased Fc{gamma} receptor affinity enhances B-cell clearing in nonhuman primates.
J. Zalevsky, I. W. L. Leung, S. Karki, S. Y. Chu, E. A. Zhukovsky, J. R. Desjarlais, D. F. Carmichael, and C. E. Lawrence (2009)
Blood 113, 3735-3743
   Abstract »    Full Text »    PDF »
Tumor-Localized Ligation of CD3 and CD28 with Systemic Regulatory T-Cell Depletion Induces Potent Innate and Adaptive Antitumor Responses.
C.-H. Lee, Y.-H. Chiang, S.-E. Chang, C.-L. Chong, B.-M. Cheng, and S. R. Roffler (2009)
Clin. Cancer Res. 15, 2756-2766
   Abstract »    Full Text »    PDF »
Stabilization and humanization of a single-chain Fv antibody fragment specific for human lymphocyte antigen CD19 by designed point mutations and CDR-grafting onto a human framework.
M. Kugler, C. Stein, M. Schwenkert, D. Saul, L. Vockentanz, T. Huber, S. K. Wetzel, O. Scholz, A. Pluckthun, A. Honegger, et al. (2009)
Protein Eng. Des. Sel. 22, 135-147
   Abstract »    Full Text »    PDF »
Tumor-Induced Suppression of CTL Expansion and Subjugation by gp96-Ig Vaccination.
T. H. Schreiber, V. V. Deyev, J. D. Rosenblatt, and E. R. Podack (2009)
Cancer Res. 69, 2026-2033
   Abstract »    Full Text »    PDF »
Aggregation-resistant VHs selected by in vitro evolution tend to have disulfide-bonded loops and acidic isoelectric points.
M. Arbabi-Ghahroudi, R. To, N. Gaudette, T. Hirama, W. Ding, R. MacKenzie, and J. Tanha (2009)
Protein Eng. Des. Sel. 22, 59-66
   Abstract »    Full Text »    PDF »
Management of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
O. G. Ottmann and H. Pfeifer (2009)
Hematology 2009, 371-381
   Abstract »    Full Text »    PDF »
Current treatment standards and emerging strategies in mantle cell lymphoma.
M. Dreyling, W. Hiddemann, and for The European MCL Network (2009)
Hematology 2009, 542-551
   Abstract »    Full Text »    PDF »
Potent In vitro and In vivo Activity of an Fc-Engineered Anti-CD19 Monoclonal Antibody against Lymphoma and Leukemia.
H. M. Horton, M. J. Bernett, E. Pong, M. Peipp, S. Karki, S. Y. Chu, J. O. Richards, I. Vostiar, P. F. Joyce, R. Repp, et al. (2008)
Cancer Res. 68, 8049-8057
   Abstract »    Full Text »    PDF »
New Approach to T-Cell Therapy for Cancer.
(2008)
Journal Watch (General) 2008, 3
   Full Text »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)