Advances in immunotherapy delivery from implantable and injectable biomaterials

Macroscale biomaterials, such as preformed implantable scaffolds and injectable soft materials, possess powerful synergies with anti-cancer immunotherapies. Immunotherapies on their own typically have poor delivery properties, and often require repeated high-dose injections that result in serious off-tumor effects and/or limited efficacy. Rationally designed biomaterials allow for discrete localization and controlled release of immunotherapeutic agents, and have been shown in a large number of applications to improve outcomes in the treatment of cancers via immunotherapy. Among various strategies, macroscale biomaterial delivery systems can take the form of robust tablet-like scaffolds that are surgically implanted into a tumor resection site, releasing programmed immune cells or immunoregulatory agents. Alternatively they can be developed as soft gel-like materials that are injected into solid tumors or sites of resection to stimulate a potent anti-tumor immune response. Biomaterials synthesized from diverse components such as polymers and peptides can be combined with any immunotherapy in the modern toolbox, from checkpoint inhibitors and stimulatory adjuvants, to cancer antigens and adoptive T cells, resulting in unique synergies and improved therapeutic efficacy. The field is growing rapidly in size as publications continue to appear in the literature, and biomaterial-based immunotherapies are entering clinical trials and human patients. It is unarguably an exciting time for cancer immunotherapy and biomaterial researchers, and further work seeks to understand the most critical design considerations in the development of the next-generation of immunotherapeutic biomaterials. This review will discuss recent advances in the delivery of immunotherapies from localized biomaterials, focusing on macroscale implantable and injectable systems. STATEMENT OF SIGNIFICANCE: Anti-cancer immunotherapies have shown exciting clinical results in the past few decades, yet they suffer from a few distinct limitations, such as poor delivery kinetics, narrow patient response profiles, and systemic side effects. Biomaterial systems are now being developed that can overcome many of these problems, allowing for localized adjuvant delivery, focused dose concentrations, and extended therapy presentation. The field of biocompatible carrier materials is uniquely suited to be combined with immunotherapy, promising to yield significant improvements in treatment outcomes and clinical care. In this review, the first pioneering efforts and most recent advances in biomaterials for immunotherapeutic applications are explored, with a specific focus on implantable and injectable biomaterials such as porous scaffolds, cryogels, and hydrogels.