David Francis

Immune checkpoint blockade (ICB) has emerged in recent years as one of the most promising classes of new cancer therapies. However, a significant majority of patients receiving these therapies 1) do not respond, 2) experience adverse side effects, or 3) respond initially but relapse. Overcoming these limitations is therefore a critical hurdle in improving cancer outcomes using ICB. To this end, immune checkpoints are active in the tumor microenvironment where they prevent T cell cytotoxic function. To date, however, clinical applications of ICB have relied on systemic administration of free antibody drugs, which results in poor accumulation in tumors and increases the risk of off target toxicities. Improving the selective delivery of ICB therapies to the tumor offers a promising approach to augment both the efficacy and safety of ICB. Moreover, upregulation of non-redundant immunosuppressive pathways is hypothesized to result in disease recurrence, motivating the use of combination immunotherapies to prevent relapse. However, many promising immunomodulatory agents that could work in synergy with ICB are small molecules and are thus short-lived in vivo, insoluble in aqueous solvents, and not targeted to the cells of interest. My work focuses on 1) improve the effects of ICB within tumor using various routes of administration and 2) develop a drug-eluting ICB platform that improves delivery of small molecule immunomodulators to T cells while simultaneously blocking immune checkpoint signaling.