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Monoclonal TCR-redirected tumor cell killing

Liddy, Nathaniel, Bossi, Giovanna, Adams, Katherine J., Lissina, Anna, Mahon, Tara M., Hassan, Namir J., Gavarret, Jessie, Bianchi, Frayne C., Pumphrey, Nicholas J., Ladell, Kristin Ingrid, Gostick, Emma, Sewell, Andrew K., Lissin, Nikolai M., Harwood, Naomi E., Molloy, Peter E., Li, Yi, Cameron, Brian J., Sami, Malkit, Baston, Emma E., Todorov, Penio T., Paston, Samantha J., Dennis, Rebecca E., Harper, Jane V., Dunn, Steve M., Ashfield, Rebecca, Johnson, Andy, McGrath, Yvonne, Plesa, Gabriela, June, Carl H., Kalos, Michael, Price, David, Vuidepot, Annelise, Williams, Daniel D., Sutton, Deborah H. and Jakobsen, Bent K 2012. Monoclonal TCR-redirected tumor cell killing. Nature Medicine 18 (6) , pp. 980-987. 10.1038/nm.2764

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: Nature Publishing Group
ISSN: 1078-8956
Date of Acceptance: 17 October 2011
Last Modified: 06 Oct 2017 14:14
URI: http://orca.cf.ac.uk/id/eprint/41572

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