Significance There is considerable interest in developing immunosuppressants that can specifically target effector memory T cells which are key to the pathogenesis of many inflammatory disorders. The potassium channel Kv1.3 has been found to play an important role in T _EM activation, but not in naive and central memory T cells. It has proven challenging to generate small molecules or antibodies that potently and selectively block Kv1.3 function. We generated antibody fusions by grafting potent Kv1.3 blocking peptides into complementary-determining regions (CDRs) of humanized antibodies, and among those, identified a candidate with high in vitro potency, excellent physiochemical and pharmacologic properties, and in vivo efficacy in a rat model. These novel toxin-antibody fusions have therapeutic potential for a variety of T _EM -mediated inflammatory diseases.