Antibody-calcineurin inhibitor conjugates that target T-cells to target refractory inflammation

National Center For Advancing Translational Sciences

Investigators

Abstract

To start this project, we will conjugate an antibody able to selectively bind with CD4 receptor and induce endocytosis. This antibody will be conjugated with tacrolimus or with a JAK2 inhibitor to block the signal facilitating inflammation, with the aim of producing selective anti-inflammatory therapy for glucocorticoid-refractory CD4 T cells. Currently we have already produced the anti-CD4 antibody able to induce endocytosis in T helper cells and we also have the chemical methodology to produce the cargo (calcinurin inhibitor or JACK2 inhibitor) containing a lysosomal cleavable sequence and a linker with a terminal acelylene for click chemistry conjugation. We have also developed a methodology able to trimp the sugars at the FC domain of the antibody and transfer an azide containing sugar to facilitate the click chemistry conjugation.