| Autor: |
David R. Stover, Dennis Benjamin, Pia Challita-Eid, Ingrid B.J. Joseph, Fernando Doñate, Daniel S. Pereira, Ying Li, Jeffrey Coleman, Steven Duniho, Ruth Moser, Faisal Malik, Claudia Guevara, Hector Aviña, Rossana Nadell, Jimmy Ou, Monica Leavitt, Alla Verlinsky, Linnette Capo, Zili An, Karen Morrison, Kendall Morrison, Arthur Raitano, Michael Mattie |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1535-7163.c.6538426.v1 |
| Popis: |
Here, we report the development of an antibody–drug conjugate, ASG-5ME, which targets the solute carrier receptor SLC44A4. SLC44A4 is a member of a family of putative choline transporters that we show to be markedly upregulated in a variety of epithelial tumors, most notably prostate and pancreatic cancer. SLC44A4 is normally expressed on the apical surface of secretory epithelial cells, but in cancer we show expression is not restricted to the luminal surface in advanced and undifferentiated tumors. ASG-5ME consists of a human IgG2 anti-SLC44A4 antibody conjugated through a cleavable linker to the microtubule-disrupting agent monomethylauristatin E. It has potent antitumor activity in both cell line – and patient-derived xenograft models of pancreatic and prostate cancers. Combination studies with ASG-5ME and nab-paclitaxel demonstrated combination effect in both pancreatic and prostate tumor models. Altogether, the data presented here suggest that ASG-5ME may have the potential to offer a new therapeutic option for the treatment of pancreatic and prostate cancers. Mol Cancer Ther; 15(11); 2679–87. ©2016 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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