Systemic T Cell–independent Tumor Immunity after Transplantation of Universal Receptor–modified Bone Marrow into SCID Mice
| Autor: | Mitchell H. Finer, Krisztina M. Zsebo, Margo R. Roberts, Kristen Hege, Keegan Cooke |
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| Rok vydání: | 1996 |
| Předmět: |
Cytotoxicity
Immunologic Male Neutrophils T-Lymphocytes T cell Transplantation Heterologous Immunology Receptors Antigen T-Cell Mice SCID Biology Polymerase Chain Reaction Article Cell Line Mice Immune system medicine Animals Humans Immunology and Allergy Receptor Bone Marrow Transplantation DNA Primers Graft Survival Gene Products env HIV Membrane Proteins Articles Transplantation Haematopoiesis medicine.anatomical_structure CD4 Antigens Female Bone marrow Stem cell Ex vivo |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.184.6.2261 |
| Popis: | Gene modification of hematopoietic stem cells (HSC) with antigen-specific, chimeric, or "universal" immune receptors (URs) is a novel but untested form of targeted immunotherapy. A human immunodeficiency virus (HIV) envelope-specific UR consisting of the extracellular domain of human CD4 linked to the zeta chain of the T cell receptor (CD4 zeta) was introduced ex vivo into murine HSC by retroviral transduction. After transplantation into immunodeficient SCID mice, sustained high level expression of CD4 zeta was observed in circulating myeloid and natural killer cells. CD4 zeta-transplanted mice were protected from challenge with a lethal dose of a disseminated human leukemia expressing HIV envelope. These results demonstrate the ability of chimeric receptors bearing zeta-signaling domains to activate non-T cell effector populations in vivo and thereby mediate systemic immunity. |
| Databáze: | OpenAIRE |
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