Hydrogel drug delivery systems for minimally invasive local immunotherapy of cancer

Although systemic immunotherapy has achieved durable responses and improved survival for certain patients and cancer types, low response rates and immune system-related systemic toxicities limit its overall impact. Intratumoral (intralesional) delivery of immunotherapy is a promising technique to combat mechanisms of tumor immune suppression within the tumor microenvironment and reduce systemic drug exposure and associated side effects. However, intratumoral injections are prone to variable tumor drug distribution and leakage into surrounding tissues, which can compromise efficacy and contribute to toxicity. Controlled release drug delivery systems such as in situ-forming hydrogels are promising vehicles for addressing these challenges by providing improved spatio-temporal control of locally administered immunotherapies with the goal of promoting systemic tumor-specific immune responses and abscopal effects. In this review we will discuss concepts, applications, and challenges in local delivery of immunotherapy using controlled release drug delivery systems with a focus on intratumorally injected hydrogel-based drug carriers.