Local scaffold-assisted delivery of immunotherapeutic agents for improved cancer immunotherapy

[Display omitted] Cancer immunotherapy, which reprograms a patient’s own immune system to eradicate cancer cells, has been demonstrated as a promising therapeutic strategy clinically. Immune checkpoint blockade (ICB) therapies, cytokine therapies, cancer vaccines, and chimeric antigen receptor (CAR) T cell therapies utilize immunotherapy techniques to relieve tumor immune suppression and/or activate cellular immune responses to suppress tumor growth, metastasis and recurrence. However, systemic administration is often hampered by limited drug efficacy and adverse side effects due to nonspecific tissue distribution of immunotherapeutic agents. Advancements in local scaffold-based delivery systems facilitate a controlled release of therapeutic agents into specific tissue sites through creating a local drug reservoir, providing a potent strategy to overcome previous immunotherapy limitations by improving site-specific efficacy and minimizing systemic toxicity. In this review, we summarized recent advances in local scaffold-assisted delivery of immunotherapeutic agents to reeducate the immune system, aiming to amplify anticancer efficacy and minimize immune-related adverse events. Additionally, the challenges and future perspectives of local scaffold-assisted cancer immunotherapy for clinical translation and applications are discussed.