T Cell Costimulus-Independent and Very Efficacious Inhibition of Tumor Growth in Mice Bearing Subcutaneous or Leukemic Human B Cell Lymphoma Xenografts by a CD19-/CD3- Bispecific Single-Chain Antibody Construct
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We have recently demonstrated that a recombinant single-chain bispecific Ab construct, bscCD19xCD3, in vitro induces rapid B lymphoma-directed cytotoxicity at picomolar concentrations with unstimulated peripheral T cells. In this study, we show that treatment of nonobese diabetic SCID mice with submicrogram doses of bscCD19xCD3 could prevent growth of s.c. human B lymphoma xenografts and essentially cured animals when given at an early tumor stage. The effect was dose dependent, dependent on E:T ratio and the time between tumor inoculation and administration of bscCD19xCD3. No therapeutic effect was seen in the presence of human lymphocytes alone, a vehicle control, or with a bispecific single-chain construct of identical T cell-binding activity but different target specificity. In a leukemic nonobese diabetic SCID mouse model, treatment with bscCD19xCD3 prolonged survival of mice in a dose-dependent fashion. The human lymphocytes used as effector cells in both animal models did not express detectable T cell activation markers at the time of coinoculation with tumor cells. The bispecific Ab therefore showed an in vivo activity comparable to that observed in cell culture with respect to high potency and T cell costimulus independence. These properties make bscCD19xCD3 superior to previously investigated CD19 bispecific Ab-based therapies.
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In preclinical trials, Dreier et al. demonstrated that submicrogram amounts of blinatumomab were sufficient to prevent tumor growth in a mouse model.
“In preclinical trials, Dreier et al. demonstrated that submicrogram amounts of this molecule were sufficient to prevent tumor growth in a mouse model. 52”
From Bispecific antibodies for cancer therapy: The light at the end of the tunnel? (2009) · cites this paper as [52]
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- Authors
- Dreier, T., Baeuerle, P. A., Fichtner, I., Grün, M., Schlereth, B., Lorenczewski, G., Kufer, P., Lutterbüse, R., Riethmüller, G., Gjorstrup, P., & Bargou, R. C.
- Affiliations
- Micromet AG , Munich ,
- Max Delbrück Center (DE)
- Institute for Immunology, Ludwig-Maximilians University , Munich ,
- Corresponding author
- Dreier, Torsten
- Schlereth, Bernd
- Lorenczewski, Grit
- Kufer, Peter
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-04
- Volume
- 170
- Issue
- 8
- Pages
- 4397-4402
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1529239585
- Cited by
- 191
- References
- 39
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 12 · 2023: 9 · 2022: 5 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 7 · 2017: 9 · 2016: 6 · 2015: 14 · 2014: 12 · 2013: 11 · 2012: 15
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (KFO 105)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- bispecific single-chain antibody, CD19, CD3, B-cell lymphoma, tumor growth inhibition, leukemia xenograft, T cell activation, cancer immunotherapy
- MeSH terms
- Animals, Antineoplastic Agents, Cells, Cultured, Graft Survival, Growth Inhibitors, Humans, Injections, Intravenous, Injections, Subcutaneous, Lymphocyte Activation, Neoplasm Transplantation, Skin Neoplasms, Time Factors, Transplantation, Heterologous, Tumor Cells, Cultured, Leukemia, B-Cell, T-Lymphocyte Subsets, Lymphoma, B-Cell, Mice, SCID, Mice, Inbred NOD, CD3 Complex, Antibodies, Bispecific, Antigens, CD19, Mice
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