Redirecting Circulating Antibodies via Ligand-Hapten Conjugates Eliminates Target Cells In Vivo
| Autor: | L. Fanget, Gao L, S Peretto, A R Lussow, Buelow R, P Pouletty |
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| Rok vydání: | 1996 |
| Předmět: |
Cytotoxicity
Immunologic Cancer Research T-Lymphocytes Immunology Mast-Cell Sarcoma Antigen-Antibody Complex Ligands Antibodies Mice chemistry.chemical_compound Immune system Antibody Specificity In vivo Tumor Cells Cultured Animals Immunology and Allergy Fluorescein isothiocyanate Antilymphocyte Serum Pharmacology Mice Inbred BALB C biology Chemistry Complement System Proteins In vitro Thymocyte Biochemistry Polyclonal antibodies biology.protein Female Immunotherapy Antibody Haptens Hapten Fluorescein-5-isothiocyanate |
| Zdroj: | Journal of Immunotherapy. 19:257-265 |
| ISSN: | 1524-9557 |
| DOI: | 10.1097/00002371-199607000-00002 |
| Popis: | The elimination of cell populations in vivo often relies on reagents that are self-limiting, are difficult to design and produce or contain highly toxic components. Here we describe a novel immunotherapy using molecules that combine a cell-specific ligand and a hapten binding to preexisting antibodies in serum. The F(ab')2 fragment of a polyclonal anti-thymocyte globulin (ATG) preparation was used as a T-cell-specific ligand, and fluorescein isothiocyanate (FITC), as the hapten. Clearance of ligand-hapten conjugates from the circulation through formation of immune complexes was prevented through controlled synthesis of conjugates so that they contained one F(ab')2 fragment and one FITC molecule. Administration of a single dose of F(ab')2 or F(ab')2ATG-FITC into naive mice had no effect on the number of circulating T cells. In contrast, injection of F(ab')2ATG-FITC into mice with circulating anti-FITC antibodies resulted in the elimination of peripheral T cells. The reduction in cell numbers was equivalent to that obtained with a corresponding dose of intact ATG. Experiments in thymectomized mice demonstrated that the reduction of circulating T cells was due to target-cell elimination and not to immunomodulation or cellular sequestration. The adaptability of the model to other sources of effector antibodies and more useful ligands is discussed. |
| Databáze: | OpenAIRE |
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