Modulation of antigen-specific T cell response by a non-mitogenic anti-CD3 antibody

International Immunopharmacology
Jian LiLi Li

Abstract

Suppression of T cell response is the key to enhance graft survival and control autoimmune diseases. A mitogenic anti-CD3 monoclonal antibody (mAb), OKT3, has been used for decades to control acute rejection in organ transplantation. Although effective, the clinical use was limited by its side effects, such as cytokine release mediated by T cell activation. A low mitogenic humanized OKT3 with reduced FcR-binding (hgammaOKT3 Ala-Ala) was generated and tested in several clinical studies. Although hgammaOKT3 Ala-Ala demonstrated maintained efficacy and better safety it still activated T cells. To investigate if a non-mitogenic anti-CD3 mAb can be equally effective in immune suppression, a chimeric non-FcR-binding anti-mouse CD3 mAb (anti-CD3 IgG2a Ala-Ala) was generated. Unlike the hgammaOKT3 Ala-Ala, the mouse IgG2a Ala-Ala anti-CD3 mAb did not induce T cell activation as measured by proliferation, cytokine production and apoptosis. Nevertheless, the IgG2a Ala-Ala anti-CD3 mAb was equally effective in the inhibition of antigen-specific CD4+ T cell activation in vitro to that of the mitogenic anti-CD3 mAb (Anti-CD3 IgG2a). In vivo, the IgG2a Ala-Ala anti-CD3 mAb only induced transient reduction of peripheral and spleen T cells and...Continue Reading

References

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Citations

May 7, 2010·Hybridoma·Luis E HinojosaAlejandro López-Requena
Apr 14, 2010·Survey of Ophthalmology·Vibhavari M NaikRaymond S Douglas
Nov 17, 2009·International Immunopharmacology·Ming LvBeifen Shen
Aug 14, 2012·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·S YouL Chatenoud
Oct 1, 2010·Current Opinion in Organ Transplantation·Sylvaine You, Lucienne Chatenoud
Jul 19, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chia-Yu FanMin-Yuan Chou
Nov 2, 2018·Molecular Cancer Therapeutics·Hreinn BenonissonThorbald van Hall

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