Side effects from medicine often limit the therapeutic window and reduce overall clinical benefits. Approaches that can minimize side effects while maintaining therapeutic efficacies represent promising directions for therapeutic developments. Our lab develops stimuli- responsive systems where a physiological stimulus regulates the therapeutic efficacy of a biological drug. Such systems can shut down therapeutic effects in off-target situations and be activated upon stimulation, and therefore, increase the therapeutic window.

In this presentation, I will discuss our efforts in two disease areas. First, insulin analogs have markedly improved glycemic control in diabetics, but glycemic excursions still cause major health complications. The narrow therapeutic window of current insulin therapy makes it extremely difficult to maintain normoglycemia without risking severe hypoglycemia. We will discuss our efforts in glucose-responsive insulin development, which provides improved glycemic control in vivo.

Second, anticancer therapies often lead to serious side effects due to off-target effects. I will discuss our efforts to develop stimuli-responsive immunotherapies for cancer treatments. Such systems can reduce the off-target toxicity of anticancer drugs while maintaining therapeutic efficacy. Overall, our research aims to provide new therapeutic options that are more effective and safer for patients by exploiting the principles of peptide chemistry and stimuli-responsiveness.