Immunotherapies harness the body’s immune system to fight disease. Such therapies can help unleash an immune attack against diseased tissues but can inadvertently instigate an attack on healthy tissues. As a result, many promising immunotherapies face major toxicities, limiting their clinical use. By employing an iterative process that entails measuring, making, and modeling to manipulate immunity, we can develop effective immunotherapies for any ailment – from cancer to cardiovascular disease.

In this seminar, I will describe our effort to develop a novel intratumorally-injected treatment to fight cancer safely and effectively. Cytokines are promising cancer immunotherapies plagued by life-threatening toxicity. Injecting cytokines directly into tumors could provide a method of confining its benefits to the cancerous tissue and away from healthy tissues, but previous attempts to do this have resulted in the cytokines rapidly leaking out of the tumor and ravaging healthy tissues. To this end, we first engineered a strategy to retain cytokines injected in a tumor, thereby safely exerting their anti-tumor activity. Then, we generated a computational framework that outlines the pharmacokinetic underpinnings of an effective tumor localized immunotherapy. Lastly, we commenced a clinical trial in companion (i.e., pet) dogs with naturally-occurring cancer aimed at generating guidelines for the administration of tumor localized cytokines in humans. Together, this work powers safe and effective local immunotherapies for cancer treatment.