2000
DOI: 10.4049/jimmunol.165.11.6205
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Non-Fc Receptor-Binding Humanized Anti-CD3 Antibodies Induce Apoptosis of Activated Human T Cells

Abstract: Human trials in organ allografts have demonstrated that murine anti-CD3 mAbs are immunosuppressive. By mimicking Ag, anti-CD3 can produce T cell activation, anergy, or death. Activation of resting T cells in vivo results in dose-limiting cytokine release and is caused by Ab-mediated cross-linking of T cells and Fcγ receptor (FcR)-bearing cells. With the goal of minimizing cytokine-induced toxicity, anti-CD3 have been engineered to lower Fc binding avidity. Preclinical murine studies have indicated that non-FcR… Show more

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Cited by 88 publications
(48 citation statements)
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References 72 publications
(51 reference statements)
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“…It is, to our knowledge, the first approach using a F(ab') 2 -based technology for specific in vivo imaging of human TCR-transgenic T cells by directly targeting the TCR without any impact on the function of targeted T cells. This is of particular interest as direct targeting of the TCR complex has been previously demonstrated to have an impact on T-cell function as well as viability potentially jeopardizing therapeutic efficacy (20,30). As previously reported (22,(31)(32)(33), we also observed alterations of T-cell function and viability by the full IgG anti-TCRmu but not its 2 .…”
Section: Discussionsupporting
confidence: 71%
“…It is, to our knowledge, the first approach using a F(ab') 2 -based technology for specific in vivo imaging of human TCR-transgenic T cells by directly targeting the TCR without any impact on the function of targeted T cells. This is of particular interest as direct targeting of the TCR complex has been previously demonstrated to have an impact on T-cell function as well as viability potentially jeopardizing therapeutic efficacy (20,30). As previously reported (22,(31)(32)(33), we also observed alterations of T-cell function and viability by the full IgG anti-TCRmu but not its 2 .…”
Section: Discussionsupporting
confidence: 71%
“…Furthermore, the expression of FcR on both of the B cells was analyzed for the reason that anti-CD3 Ab-mediated activation of T cells is known to be dependent on the cross-linking of T cells by the FcRs on the accessory cells (31). Therefore, the differential levels of FcRs on B cells could also account for the observed difference in their CD8…”
Section: Expression Of Costimulatory Molecules On B Cellsmentioning
confidence: 99%
“…Durable expression of the TCR allows sustained signaling by visilizumab leading to apoptosis. 14 We hypothesized that visilizumab might produce selective clonal deletion of activated pathogenic T cells and therefore serve as an ideal agent to treat GVHD. Here we report the initial study of safety, pharmacokinetics, and immunosuppressive activity of antibody visilizumab administered to patients with glucocorticoid-refractory acute GVHD.…”
Section: Introductionmentioning
confidence: 99%