You are here:
| Reference : Efficiency of T Cell Triggering by Anti-Cd3 Monoclonal Antibodies (Mab) with Potential U... |
| Scientific journals : Article | |||
| Human health sciences : Oncology Human health sciences : Immunology & infectious disease | |||
| http://hdl.handle.net/2268/21004 | |||
| Efficiency of T Cell Triggering by Anti-Cd3 Monoclonal Antibodies (Mab) with Potential Usefulness in Bispecific Mab Generation | |
| English | |
Jacobs, Nathalie  [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >] | |
| Mazzoni, A. [> > > >] | |
| Mezzanzanica, D. [> > > >] | |
| Negri, D. R. [> > > >] | |
| Valota, O. [> > > >] | |
| Colnaghi, M. I. [> > > >] | |
| Moutschen, M. P. [> > > >] | |
| Boniver, Jacques [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques] | |
| Canevari, Silvana [Fondazione IRCCS Istituto Nazionale dei Tumori > Experimental Oncology Department > > >] | |
| Jul-1997 | |
| Cancer Immunology, Immunotherapy | |
| Springer Verlag | |
| 44 | |
| 5 | |
| 257-64 | |
| International | |
| 0340-7004 | |
| [en] Bispecific antibody ; immunotherapy ; anti-CD3 ; T-cell receptor ; cytotoxicity | |
| [en] T cell triggering can be achieved by monoclonal antibodies (mAbs) specific for the CD3/TcR complex. In the presence of appropriate costimulation and/or progression factors, such triggering permits the generation of effector cells for immunotherapy protocols involving the redirection of T cell lysis against tumor cells by mAbs bispecific for anti-CD3/anti-tumor cells (bs-mAbs). Focusing our analysis on the clinically relevant bs-mAb OC/TR, we found that bs-mAbs generated with the same anti tumor specificity, but two other anti-CD3 mAbs, TR66 and OKT3, have the same and a significantly lower lytic potential, respectively, compared with that of OC/TR. To evaluate the relevance of the anti-CD3 component, we examined several anti-CD3 mAbs with respect to binding parameters and the ability to trigger T lymphocytes. Competitive binding assays suggested that all anti-CD3 mAbs recognized the same or overlapping epitopes, although mAbs BMA030 and OC/TR bound with lower avidity than did alpha CD3 (the bivalent anti-CD3 mAb produced by the hybrid hybridoma OC/TR). TR66 and OKT3, as determined by measurement of the affinity constants. In all lymphocyte populations examined, which included resting peripheral blood mononuclear cells (PBMC), activated PBMC and T cell clones, OKT3, BMA033 and OC/TR failed to mobilize Ca2+ without cross-linking, whereas alpha CD3, in both murine and murine-human chimeric versions, TR66 and BMA030, did not require cross-linking. The ability to induce CD3 modulation was associated in part with the induction of Ca2+ fluxes. Despite the differences in the behavior of these mAbs in triggering the events that precede proliferation, all of them ultimately led to expression of the IL-2 receptor and to proliferation in T cells in the presence of accessory cells. Our data suggest that anti-CD3 mAbs that bind more rapidly (strong Ca2+ mobilizers) and more tightly under physiological conditions are good candidates for retargeting T cells in the bs-mAb clinical application. | |
| Researchers ; Students | |
| http://hdl.handle.net/2268/21004 |
| File(s) associated to this reference | ||||||||||||||
|
Fulltext file(s):
| ||||||||||||||
All documents in ORBi are protected by a user license.
