title: Monoclonal TCR-redirected tumor cell killing.
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.
authors.affiliation: Immunocore Ltd., Abingdon, Oxon, UK.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Liddy
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bossi
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Adams
authors.forename: Anna
authors.initials: A
authors.lastname: Lissina
authors.forename: Tara M
authors.initials: TM
authors.lastname: Mahon
authors.forename: Namir J
authors.initials: NJ
authors.lastname: Hassan
authors.forename: Jessie
authors.initials: J
authors.lastname: Gavarret
authors.forename: Frayne C
authors.initials: FC
authors.lastname: Bianchi
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Pumphrey
authors.forename: Kristin
authors.initials: K
authors.lastname: Ladell
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Sewell
authors.forename: Nikolai M
authors.initials: NM
authors.lastname: Lissin
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Harwood
authors.forename: Peter E
authors.initials: PE
authors.lastname: Molloy
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cameron
authors.forename: Malkit
authors.initials: M
authors.lastname: Sami
authors.forename: Emma E
authors.initials: EE
authors.lastname: Baston
authors.forename: Penio T
authors.initials: PT
authors.lastname: Todorov
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Paston
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Dennis
authors.forename: Jane V
authors.initials: JV
authors.lastname: Harper
authors.forename: Steve M
authors.initials: SM
authors.lastname: Dunn
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ashfield
authors.forename: Andy
authors.initials: A
authors.lastname: Johnson
authors.forename: Yvonne
authors.initials: Y
authors.lastname: McGrath
authors.forename: Gabriela
authors.initials: G
authors.lastname: Plesa
authors.forename: Carl H
authors.initials: CH
authors.lastname: June
authors.forename: Michael
authors.initials: M
authors.lastname: Kalos
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Annelise
authors.initials: A
authors.lastname: Vuidepot
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Williams
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Sutton
authors.forename: Bent K
authors.initials: BK
authors.lastname: Jakobsen
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma