Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells.

Abstract

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.

• Authors: Sonja Offner, Robert Hofmeister, Andrea Romaniuk, Peter Kufer, Patrick A Baeuerle
• Journal: Molecular immunology (Mol Immunol) Vol. 43 Issue 6 Pg. 763-71 (Feb 2006) ISSN: 0161-5890 [Print] England
• PMID: 16360021 (Publication Type: Journal Article)

Chemical References

• Antibodies, Bispecific
• Epitopes, T-Lymphocyte
• Histocompatibility Antigens Class I

Topics

• Antibodies, Bispecific (chemistry, immunology)
• Cell Communication (immunology)
• Cell Line, Tumor
• Coculture Techniques
• Epitopes, T-Lymphocyte (immunology)
• Histocompatibility Antigens Class I
• Humans
• Lymphocyte Activation (immunology)
• Microscopy, Confocal
• Neoplasms (immunology, pathology)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Escape