| Literature DB >> 22561687 |
Nathaniel Liddy1, Giovanna Bossi, Katherine J Adams, Anna Lissina, Tara M Mahon, Namir J Hassan, Jessie Gavarret, Frayne C Bianchi, Nicholas J Pumphrey, Kristin Ladell, Emma Gostick, Andrew K Sewell, Nikolai M Lissin, Naomi E Harwood, Peter E Molloy, Yi Li, Brian J Cameron, Malkit Sami, Emma E Baston, Penio T Todorov, Samantha J Paston, Rebecca E Dennis, Jane V Harper, Steve M Dunn, Rebecca Ashfield, Andy Johnson, Yvonne McGrath, Gabriela Plesa, Carl H June, Michael Kalos, David A Price, Annelise Vuidepot, Daniel D Williams, Deborah H Sutton, Bent K Jakobsen.
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.Entities:
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Year: 2012 PMID： 22561687 DOI： 10.1038/nm.2764
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440