2026-10-10T18:19:46Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34032306 2026-09-30T12:38:48Z category_388 portal_316 item_type_3 month_year_09_2026

Table 3_Multi-parameter optimization of a novel anti-TROP2 MMAE antibody-drug-conjugate for solid tumor therapy.xlsx Laurence Fayadat-Dilman (5474861) Andrew B. Waight (2940078) Lauren Adams (7273535) Peyman Akbari (799575) Minilik Angagaw (258952) Jeanne Baker (153141) Michelle Castor (25143915) Andy Chen (9188602) Daoyang Chen (4732431) Ming-Tang Chen (411098) Ellen Chien (17137370) Jill E. Chrencik (3615887) Darcey Clark (25143918) James Dutko (25143921) Mehabaw Derebe (25143924) Alan Goggins (25143927) Thomas Griffiths (443696) Mee Ra Heon (25143930) Marlene C. Hinton (2864213) SuChun Hsieh (1412512) Amy Hsu (3456413) Zhong L. Hua (17376358) Mark Ibrahim (6321080) Mengxuan Jia (16846659) Rebecca E. Johnson (1361724) Simon B. Lang (1933867) Su-Yang Liu (25143933) Daniel Malashock (19772649) Aleksandra Olow (14209115) Michael Oropallo (25143936) Andrea T. Partridge (25143939) Vin Penaflor (25143942) Elnaz Rasti Boroujeni (25143945) Zhao Ren (422101) Karthik Sathiyamoorthy (160368) Makiko Uchida (25143948) Derek Wiswell (2276644) Jane Xia (14928060) Peng Yang (296696) Jennifer Yearley (5505899) Sultan Yilmaz (25143951) Yao Yu (137213) John A. Flygare (1738738) Bernhard H. Geierstanger (1459717) Jianzhong Wen (2129014) W. Michael Seganish (1551463) Edward P. Bowman (14928063) Oncology and Carcinogenesis not elsewhere classified antibody-drug-conjugate avidity tuning hydrophobicity MMAE monoclonal antibody solid tumors stable linker Trop2 <p>TROP2 is expressed in many epithelial tumors including breast and lung cancers. It is a clinically validated ADC target based on approvals of sacituzumab govitecan for triple-negative breast cancer and datopotamab deruxtecan for HR-positive, HER2-negative breast cancer. An alternative cytotoxic approach was previously tested with PF-06664178/RN927C, an anti-TROP2 ADC with an auristatin payload, which entered clinical studies but could not be dosed efficaciously due to dose-limiting toxicities including skin rash, mucosal inflammation, and neutropenia. TroptimAb-SL-MMAE was engineered using an optimized anti-TROP2 sacituzumab antibody sequence (TroptimAb) to address issues related to hydrophobicity, non-specific uptake, and ADC developability. Sacituzumab was re_-humanized and modified to enhance FcRn-mediated salvage which extended systemic half-life and potentially improving tumor distribution. Its affinity was avidity-tuned to preferentially bind cells with higher TROP2 expression to reduce on-target/off-tumor toxicity. An engineered cysteine in the Fc domain enabled generation of a homogeneous DAR2 ADC and shielded the linker-payload to reduce hydrophobicity and improve biophysical properties. Linker conjugation chemistry was also optimized to improve stability versus earlier cysteine-conjugated ADCs. We describe the preclinical profile of TroptimAb-SL-MMAE including its design, mechanism of action, anti-tumor activity, and pharmacokinetics.</p> 2026-09-30T12:38:48Z Dataset Dataset 10.3389/fonc.2026.1915652.s007 https://figshare.com/articles/dataset/Table_3_Multi-parameter_optimization_of_a_novel_anti-TROP2_MMAE_antibody-drug-conjugate_for_solid_tumor_therapy_xlsx/34032306 CC BY 4.0