Summary Autoimmune uveitis is a major cause of blindness in which retinal antigen-specific T cells lead to ocular inflammation and vision loss. Similar to the treatment of other T cell-mediated autoimmune diseases, selective suppression of the pathogenic T cells is the “holy grail” of therapeutic development. In pilot studies, we have developed a novel antibody-drug conjugate (ADC) with combined T cell targeting and potent anti-mitosis activity, which is designed to selectively kill the proliferating autoreactive T cells while sparing the other cells including normal T cells. In this Phase I application, we will first demonstrate that this ADC selectively kills proliferating uveitogenic T cells while sparing normal T cells and other cells both in vitro and in vivo, then determine its in vivo treatment efficacy and potential off-target effects in two animal models of autoimmune uveitis. These studies will provide the required proof-of-concept for a Phase II development of this promising ADC towards IND-enabling studies and further clinical development.