التفاصيل البيبلوغرافية
العنوان:
Data from In Vitro and In Vivo Activity of IMGN853, an Antibody–Drug Conjugate Targeting Folate Receptor Alpha Linked to DM4, in Biologically Aggressive Endometrial Cancers
المؤلفون:
Alessandro D. Santin , Peter E. Schwartz , Masoud Azodi , Gloria S. Huang , Dan-Arin Silasi , Elena Ratner , Babak Litkouhi , Serena Wong , Pei Hui , Natalia Buza , Jose F. Ponte , Ashley Morneault , Katherine Dugan , Ghanshyam Yadav , Chanhee Han , Luca Zammataro , Jacqueline Feinberg , Francesco Riccio , Anna Bianchi , Francesca Pettinella , Gulden Menderes , Tomomi Egawa-Takata , Stefania Bellone , Elena Bonazzoli , Gary Altwerger
بيانات النشر:
American Association for Cancer Research (AACR), 2023.
سنة النشر:
2023
الوصف:
Grade 3 endometrioid and uterine serous carcinomas (USC) account for the vast majority of endometrial cancer deaths. The purpose of this study was to determine folic acid receptor alpha (FRα) expression in these biologically aggressive (type II) endometrial cancers and evaluate FRα as a targetable receptor for IMGN853 (mirvetuximab soravtansine). The expression of FRα was evaluated by immunohistochemistry (IHC) and flow cytometry in 90 endometrioid and USC samples. The in vitro cytotoxic activity and bystander effect were studied in primary uterine cancer cell lines expressing differential levels of FRα. In vivo antitumor efficacy of IMGN853 was evaluated in xenograft/patient-derived xenograft (PDX) models. Semiquantitative IHC analysis indicated that 41% of the USC patients overexpress FRα. Further, overexpression of FRα (i.e., 2+) was detected via flow cytometry in 22% (2/9) of primary endometrioid and in 27% (3/11) of primary USC cell lines. Increased cytotoxicity was seen with IMGN853 treatment compared with control in 2+ expressing uterine tumor cell lines. In contrast, tumor cell lines with low FRα showed no difference when exposed to IMGN853 versus control. IMGN853 induced bystander killing of FRα = 0 tumor cells. In an endometrioid xenograft model (END(K)265), harboring 2+ FRα, IMGN853 treatment showed complete resolution of tumors (P < 0.001). Treatment with IMGN853 in the USC PDX model (BIO(K)1), expressing 2+ FRα, induced twofold increase in median survival (P < 0.001). IMGN853 shows impressive antitumor activity in biologically aggressive FRα 2+ uterine cancers. These preclinical data suggest that patients with chemotherapy resistant/recurrent endometrial cancer overexpressing FRα may benefit from this treatment. Mol Cancer Ther; 17(5); 1003–11. ©2018 AACR.
URL الوصول:
https://explore.openaire.eu/search/publication?articleId=doi_________::a81646ed0c38f7c706dc160a71539783 https://doi.org/10.1158/1535-7163.c.6537780.v1
حقوق:
OPEN
رقم الأكسشن:
edsair.doi...........a81646ed0c38f7c706dc160a71539783
قاعدة البيانات:
OpenAIRE
