Choi, Jiwoong Jang, Hochung Choi, Jiwon Choi, Yeonho Yang, Yoosoo Shim, Man Kyu Kim, Sun Hwa 2024-01-19T09:04:37Z 2024-01-19T09:04:37Z 2023-07-13 2023-07 0168-3659 https://pubs.kist.re.kr/handle/201004/113531 Immune checkpoint blockade (ICB) therapy has shown remarkable outcomes along with multiple cases of complete regression in clinical practice. But unfortunately, most patients who have an immunosuppressive tumor immune microenvironment (TIME) respond poorly to these therapies. To improve the response rate of the patients, various treatment modalities that can boost cancer immunogenicity and remove immune tolerance have been combined with ICB therapies. However, the systemic administration of multiple immunotherapeutic agents can potentially cause severe off-target toxicities and immune-related adverse events, diminishing antitumor immunity and increasing the risk of additional complications. To address these problems, Immune CheckpointTargeted Drug Conjugates (IDCs) have been widely investigated for their ability to offer distinct advantages in remodeling the TIME for cancer immunotherapy. IDCs, consisting of immune checkpoint-targeting moieties, cleavable linkers, and payloads of immunotherapeutic agents, have a similar structure to conventional antibodydrug conjugates (ADCs) but target and block the immune checkpoint receptors, and then release the payloads conjugated through cleavable linkers. These unique mechanisms of IDCs prompt an immune-responsive TIME by modulating the multiple steps related to the cancer-immunity cycle, ultimately leading to tumor eradication. This review outlines the mode of action and advantages of IDCs. In addition, various IDCs for combinational immunotherapy are reviewed. Finally, the potential and challenges of IDCs for clinical translation are discussed. English Elsevier BV Immune checkpoint-targeted drug conjugates: A promising tool for remodeling tumor immune microenvironment Article 10.1016/j.jconrel.2023.05.031 1 Journal of Controlled Release, v.359, pp.85 - 96 Journal of Controlled Release 359 85 96 N scie scopus 001014652500001 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article IMMUNOGENIC CELL-DEATH CANCER-IMMUNOTHERAPY RNA INTERFERENCE EMERGING ROLES ADVERSE EVENTS CATHEPSIN-B IN-VIVO BLOCKADE NANOBODY PD-L1 Cancer immunotherapy Immune checkpoint blockade Tumor immune microenvironment Drug conjugate Combinational immunotherapy