Monoclonal TCR-redirected tumor cell killing
| Autor: | Jessie Gavarret, Katherine Adams, Jane Harper, Bent K. Jakobsen, Yi Li, Frayne Bianchi, Emma Baston, Michael Kalos, Penio Todorov, Malkit Sami, Steve M. Dunn, Emma Gostick, Nikolai Lissin, David Price, Rebecca Dennis, Peter Eamon Molloy, Samantha Paston, Gabriela Plesa, Kristin Ladell, Giovanna Bossi, Namir J. Hassan, Deborah H. Sutton, Naomi Harwood, Annelise Vuidepot, Carl H. June, Nicholas J. Pumphrey, Nathaniel Liddy, Yvonne McGrath, Brian Cameron, Daniel Williams, Andrew K. Sewell, Tara Mahon, Rebecca Ashfield, Anna Lissina, Andrew M.F. Johnson |
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| Rok vydání: | 2012 |
| Předmět: |
Cytotoxicity
Immunologic medicine.medical_treatment T cell CD3 Receptors Antigen T-Cell chemical and pharmacologic phenomena Mice SCID CD8-Positive T-Lymphocytes Biology Lymphocyte Activation General Biochemistry Genetics and Molecular Biology Epitope Interferon-gamma Mice Antigen medicine Animals Humans T-cell receptor Neoplasms Experimental General Medicine Immunotherapy medicine.anatomical_structure Immunology Monoclonal Cancer research biology.protein Antibody Immunologic Memory |
| Zdroj: | Nature Medicine. 18:980-987 |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | T cell immunity can potentially eradicate malignant cells and lead to clinical remission in a minority of patients with cancer. In the majority of these individuals, however, there is a failure of the specific T cell receptor (TCR)–mediated immune recognition and activation process. Here we describe the engineering and characterization of new reagents termed immune-mobilizing monoclonal TCRs against cancer (ImmTACs). Four such ImmTACs, each comprising a distinct tumor-associated epitope-specific monoclonal TCR with picomolar affinity fused to a humanized cluster of differentiation 3 (CD3)-specific single-chain antibody fragment (scFv), effectively redirected T cells to kill cancer cells expressing extremely low surface epitope densities. Furthermore, these reagents potently suppressed tumor growth in vivo. Thus, ImmTACs overcome immune tolerance to cancer and represent a new approach to tumor immunotherapy. |
| Databáze: | OpenAIRE |
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