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
| Autor: | Grit Lorenczewski, Michael Grün, Bernd Schlereth, Ralf C. Bargou, Iduna Fichtner, Per Gjorstrup, Gert Riethmüller, Patrick A. Baeuerle, Torsten Dreier, Ralf Lutterbüse, Peter Kufer |
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| Rok vydání: | 2003 |
| Předmět: |
Lymphoma
B-Cell Skin Neoplasms Time Factors CD3 Complex Injections Subcutaneous CD3 T cell Antigens CD19 Transplantation Heterologous Immunology Antineoplastic Agents Mice SCID Lymphocyte Activation CD19 Mice Antigen Mice Inbred NOD T-Lymphocyte Subsets In vivo Antibodies Bispecific Leukemia B-Cell Tumor Cells Cultured medicine Animals Humans Immunology and Allergy Cytotoxicity Cells Cultured biology Graft Survival Growth Inhibitors Transplantation medicine.anatomical_structure Injections Intravenous biology.protein Cancer research Antibody Neoplasm Transplantation |
| Zdroj: | The Journal of Immunology. 170:4397-4402 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.170.8.4397 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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