Project Description: Immunotherapeutic interventions are providing substantial therapeutic benefit for many cancer patients. However, immunotherapies can unleash an immune attack against not only tumors but also healthy tissues. As a result, many promising immunotherapies, such as cytokines, face dose-limiting toxicities which curb their efficacy and clinical translation. An enduring challenge in the field is to improve the therapeutic index of these agents.
To address this problem, we developed a platform for intratumoral localization of immunomodulatory payloads like cytokines via fusion to collagen-binding modules. We find that intratumorally-injected cytokines that are retained on collagen and large in molecular size can exert profound therapeutic effects while largely sparing from systemic exposure or toxicity. Now, we aim to examine the micropharmacokinetics rules of intratumoral delivery and collagen-anchoring in order to inform improvements to our collagen-retained therapies and the numerous clinical agents that are also locally administered.