Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells.
Certain bispecific single-chain antibody constructs exhibit an extraordinary potency for polyclonal T cell engagement and target cell lysis. Here we studied the structural basis for this potency, using laser scanning confocal microscopy. Cytolytic human T cell synapses could be triggered either by addition of a specific peptide antigen or an Ep-CAM-/CD3-bispecific T cell engager (BiTE). Both kinds of synapses showed a comparable distribution of all protein markers investigated. Two other BiTEs constructed from different Ep-CAM-specific antibodies gave similar results. BiTEs could also induce lytic synapses between human T cells and a MHC class I-negative, Ep-CAM cDNA-transfected cell line resulting in potent target cell lysis. This shows that certain T cell recognition molecules on target cells are dispensable for synapse formation and BiTE activity, and suggests that BiTE-activated polyclonal T cells may ignore major immune evasion mechanisms of tumor cells in vivo, such as loss of MHC class I expression.
Offner
Sonja
S
Micromet AG, Staffelseestr. 2, 81477 Munich, Germany.
Hofmeister
Robert
R
Romaniuk
Andrea
A
Kufer
Peter
P
Baeuerle
Patrick A
PA
D018033:Antibodies, Bispecific / Q000737:chemistry / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015395:Histocompatibility Antigens Class I; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019139:Tumor Escape
D018033:Antibodies, Bispecific; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I