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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.

Original publication

DOI

10.1038/nm.2764

Type

Journal article

Journal

Nat Med

Publication Date

06/2012

Volume

18

Pages

980 - 987

Keywords

Animals, CD8-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Humans, Immunologic Memory, Immunotherapy, Interferon-gamma, Lymphocyte Activation, Mice, Mice, SCID, Neoplasms, Experimental, Receptors, Antigen, T-Cell