Breakthroughs in molecular mechanisms underlying immune-suppressive tumor microenvironment and paradigm shifts in the cancer-immunity response cycle have profoundly changed the landscape of cancer immunotherapy. However, one of the challenges is to mitigate the serious side effects caused by systemic autoimmunity and autoinflammatory responses following immunotherapy. Thus, restraining the activation of the immune system in healthy tissues is highly desirable to address this problem. Bioengineering and delivery technologies provide a solution to the issue. In this Review, we first introduce immune-related adverse effects of main immunotherapies and the underlying mechanisms, summarize strategies of designingde bioengineering and delivery systems to reduce their immunotoxicities, and highlight the importance of the development of immunotoxicity-related animal models.
Keywords: Chimeric antigen receptor T cell (CAR-T); Cytokines; Immune checkpoint inhibitors; Immunotoxicity; Preclinical animal models; Targeted delivery.
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