Hydrogel-enabled, local administration and combinatorial delivery of immunotherapies for cancer treatment

Throughout the last decade, interventions to engineer the immune system called immunotherapy have revolutionized the fields of oncology and autoimmune disease. Researchers are developing platforms that enable new modes of immunotherapy and expand the current limitations by incorporating non-intravenous delivery strategies. Recent advances in the immunotherapy include the use of chemokines to direct immune cells into tumors, alternative combinatorial therapies, and oncolytic viruses. Similarly, there have been significant breakthroughs in the design and understanding of new biocompatible hydrogel-based materials for diverse biomedical applications, including large molecule drug delivery. In this review, we discuss how hydrogel platforms can enable modes of immunotherapy that are otherwise not feasible. Despite the many pre-clinical successes of hydrogels for the delivery of immunotherapies for treatment of cancer, hydrogels still face challenges in getting to the clinic and eventually approved. Herein we examine the application of hydrogels in high concentration subcutaneous, intratumoral, peritumoral, intraperitoneal, intracranial, and pulmonary delivery of immunotherapies. By analyzing the results of many pre-clinical hydrogel-enabled immunotherapy studies, we describe that local hydrogel delivery is a promising approach to increase the efficacy and decrease systemic toxicities of immunotherapies. We also discuss the application of hydrogels for synergistic combinatorial immunotherapy. Furthermore, we summarize the advancements and obstacles in local intratumoral administration and sustained release of immunotherapy-loaded hydrogels. Finally, we discuss challenges in the translational research, clinical development, and manufacturing of hydrogels which must be addressed to advance the field.