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 Checkpoint-Targeted 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 antibody-drug 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.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation (NRF) of South Korea, funded by the Ministry of Science ( NRF-2021R1C1C2005460 and NRF-2022M3E5F1018529 ) of Republic of Korea, the KU-KIST Graduate School of Converging Science and Technology (Korea University), and the Intramural Research Program of KIST .
© 2023 Elsevier B.V.
- Cancer immunotherapy
- Combinational immunotherapy
- Drug conjugate
- Immune checkpoint blockade
- Tumor immune microenvironment
ASJC Scopus subject areas
- Pharmaceutical Science