{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["5(5)"],"submitter":["Shi W"],"funding":["Shanghai Chest Hospital of Shanghai Jiao Tong University School of Medicine","Shanghai Jiao Tong University"],"pubmed_abstract":["The clinical applications of immunocytokines are severely restricted by dose-limiting toxicities. To address this challenge, here we propose a next-generation immunocytokine concept involving the design of LH05, a tumor-conditional anti-PD-L1/interleukin-15 (IL-15) prodrug. LH05 innovatively masks IL-15 with steric hindrance, mitigating the \"cytokine sink\" effect of IL-15 and reducing systemic toxicities associated with wild-type anti-PD-L1/IL-15. Moreover, upon specific proteolytic cleavage within the tumor microenvironment, LH05 releases an active IL-15 superagonist, exerting potent antitumor effects. Mechanistically, the antitumor efficacy of LH05 depends on the increased infiltration of CD8<sup>+</sup> T and natural killer cells by stimulating the chemokines CXCL9 and CXCL10, thereby c"],"journal":["Cell reports. Medicine"],"pagination":["101531"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11148641"],"repository":["biostudies-literature"],"pubmed_title":["Next-generation anti-PD-L1/IL-15 immunocytokine elicits superior antitumor immunity in cold tumors with minimal toxicity."],"pmcid":["PMC11148641"],"pubmed_authors":["Zhou L","Wu M","Zeng Q","Jiang L","Chen J","Liu N","Zhu F","Shi W","Song L","Hu F","Liu Z","Yang Y","Zhu J","Lu H","Fu J","Gong L","Wang Y"],"additional_accession":[]},"is_claimable":false,"name":"Next-generation anti-PD-L1/IL-15 immunocytokine elicits superior antitumor immunity in cold tumors with minimal toxicity.","description":"The clinical applications of immunocytokines are severely restricted by dose-limiting toxicities. To address this challenge, here we propose a next-generation immunocytokine concept involving the design of LH05, a tumor-conditional anti-PD-L1/interleukin-15 (IL-15) prodrug. LH05 innovatively masks IL-15 with steric hindrance, mitigating the \"cytokine sink\" effect of IL-15 and reducing systemic toxicities associated with wild-type anti-PD-L1/IL-15. Moreover, upon specific proteolytic cleavage within the tumor microenvironment, LH05 releases an active IL-15 superagonist, exerting potent antitumor effects. Mechanistically, the antitumor efficacy of LH05 depends on the increased infiltration of CD8<sup>+</sup> T and natural killer cells by stimulating the chemokines CXCL9 and CXCL10, thereby c","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-02T09:05:12.358Z","creation":"2026-04-16T03:13:05.316Z"},"accession":"S-EPMC11148641","cross_references":{"pubmed":["38697105"],"doi":["10.1016/j.xcrm.2024.101531"]}}