{"id":"doi:10.18632/oncotarget.4318","kind":"article","title":"Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC)","authors":["Goldenberg DM","Cardillo TM","Govindan SV","Rossi EA","Sharkey RM"],"author_count":5,"year":2015,"published":"2015-09-01","venue":"Oncotarget","cited_by":411,"doi":"10.18632/oncotarget.4318","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.18632/oncotarget.4318","archive_url":"https://space-kitty.com/papers/doi:10.18632/oncotarget.4318","updated":null,"pmid":"26101915","pmcid":"PMC4673178","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC4673178/pdf","abstract":"Trop-2 is a novel target for ADC therapy because of its high expression by many solid cancers. The rational development of IMMU-132 represents a paradigm shift as an ADC that binds a well-known moderately-cytotoxic drug, SN-38, to the anti-Trop-2 antibody. In vitro and in vivo studies show enhanced efficacy, while there is a gradual release of SN-38 that contributes to the overall effect. IMMU-132 is most efficacious at a high drug:antibody ratio (DAR) of 7.6:1, which does not affect binding and pharmacokinetics. It targets up to 136-fold more SN-38 to a human cancer xenograft than irinotecan, SN-38's prodrug. IMMU-132 delivers SN-38 in its most active, non-glucuronidated form, which may explain the lower frequency of severe diarrhea than with irinotecan. Thus, this ADC, carrying a moderately-toxic drug targeting Trop-2 represents a novel cancer therapeutic that is showing promising activity in patients with several metastatic cancer types, including triple-negative breast cancer, non-small-cell and small-cell lung cancers.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC)\" by Goldenberg DM, Cardillo TM, Govindan SV et al., https://doi.org/10.18632/oncotarget.4318, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"cancer-immunotherapy","name":"Cancer Immunotherapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}