Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: Conditional knockdown of the receptor in tumor xenograft models resulted in only a modest impact on tumor growth. A monoclonal antibody reactive with the N-terminal tail of EDNBR was found to internalize rapidly into melanoma cells. When conjugated with monomethyl auristatin E, the antibody-drug conjugate (ADC) showed remarkable efficacy against human melanoma cell lines and xenograft tumor models that was commensurate with levels of receptor expression. Comparative immunohistochemistry revealed a range of EDNBR expression across a panel of human melanomas, with the majority expressing levels equivalent to or greater than that in the models responsive to the ADC. CONCLUSION: An ADC targeting the EDNBR is highly efficacious in preclinical models of melanoma.
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Authors | Jyoti Asundi, Chae Reed, Jennifer Arca, Krista McCutcheon, Ronald Ferrando, Suzanna Clark, Elizabeth Luis, Janet Tien, Ron Firestein, Paul Polakis |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 17
Issue 5
Pg. 965-75
(Mar 01 2011)
ISSN: 1557-3265 [Electronic] United States |
PMID | 21245091
(Publication Type: Journal Article)
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Copyright | ©2011 AACR. |
Chemical References |
- Antibodies, Monoclonal
- Antineoplastic Agents
- Endothelin B Receptor Antagonists
- Immunoconjugates
- Microphthalmia-Associated Transcription Factor
- Oligopeptides
- RNA, Messenger
- Receptor, Endothelin B
- monomethyl auristatin E
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Topics |
- Animals
- Antibodies, Monoclonal
(therapeutic use)
- Antineoplastic Agents
(therapeutic use)
- Blotting, Western
- Cell Line, Tumor
- Endothelin B Receptor Antagonists
- Flow Cytometry
- Fluorescent Antibody Technique
- Gene Expression
- Gene Knockdown Techniques
- Humans
- Immunoconjugates
(therapeutic use)
- Macaca fascicularis
- Melanoma
(drug therapy, genetics, immunology)
- Melanoma, Experimental
(drug therapy, genetics, immunology)
- Mice
- Mice, Inbred BALB C
- Microphthalmia-Associated Transcription Factor
(genetics)
- Oligopeptides
(administration & dosage, therapeutic use)
- RNA, Messenger
(genetics, metabolism)
- Rats
- Receptor, Endothelin B
(immunology)
- Xenograft Model Antitumor Assays
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