Controlled release of immunotherapeutics for enhanced cancer immunotherapy after local delivery

Cancer immunotherapy has been demonstrated as a promising therapeutic strategy in clinic owing to its unique advantages. However, although more and more immunotherapeutic agents have been approved for clinical use to activate the immune system, they also could interfere with the homeostatic role of immune system at non-target sites after systemic administration, which may be associated with fatal side effects such as lifelong autoimmune diseases. Thus, it is desirable to develop local delivery systems that could be applied at the targeted sides and engineered to locally control the pharmacokinetics of various immunotherapeutics, including small molecules, macromolecules or even cells. Advancements in biomaterials, biotechnology, nanomedicine and engineering have facilitated the development of local delivery systems for enhanced cancer immunotherapy. This review will summarize the recent advances in developing different local delivery systems and discuss how these delivery systems could be designed to regulate the release behavior of different immunotherapeutics to sustainably stimulate the systemic immune system, effectively and safely inhibiting the cancer recurrence and metastasis. Furthermore, we will discuss how biomaterials-assisted local delivery systems would contribute to the development of cancer immunotherapy, together with their challenges and potential of clinical translation.