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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2020 | Melanoma | Research

Characterization of novel neutralizing mouse monoclonal antibody JM1-24-3 developed against MUC18 in metastatic melanoma

Authors: Runhua Feng, Yuling Wang, Vijaya Ramachandran, Qinhong Ma, Matthew M. May, Ming Li, Joe X. Zhou, Xiang Xu, Kejing Xu, Shenying Fang, Weiya Xia, Dawen Sui, Huey Liu, Xiaolian Gao, Victor Prieto, Stephen C. Blacklow, Mason Lu, Jeffrey E. Lee

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2020

Abstract

Background

MUC18 is a glycoprotein highly expressed on the surface of melanoma and other cancers which promotes tumor progression and metastasis. However, its mechanism of action and suitability as a therapeutic target are unknown.

Methods

A monoclonal antibody (mAb) (JM1-24-3) was generated from metastatic melanoma tumor live cell immunization, and high-throughput screening identified MUC18 as the target.

Results

Analysis of molecular interactions between MUC18 and JM1-24-3 revealed that the downstream signaling events depended on binding of the mAb to a conformational epitope on the extracellular domain of MUC18. JM1-24-3 inhibited melanoma cell proliferation, migration and invasion in vitro and reduced tumor growth and metastasis in vivo.

Conclusion

These results confirm that MUC18 is mechanistically important in melanoma growth and metastasis, suggest that the MUC18 epitope identified is a promising therapeutic target, and that the JM1-24-3 mAb may serve as the basis for a potential therapeutic agent.

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Title: Characterization of novel neutralizing mouse monoclonal antibody JM1-24-3 developed against MUC18 in metastatic melanoma
Authors: Runhua Feng
Yuling Wang
Vijaya Ramachandran
Qinhong Ma
Matthew M. May
Ming Li
Joe X. Zhou
Xiang Xu
Kejing Xu
Shenying Fang
Weiya Xia
Dawen Sui
Huey Liu
Xiaolian Gao
Victor Prieto
Stephen C. Blacklow
Mason Lu
Jeffrey E. Lee
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Melanoma
Melanoma
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2020
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-020-01722-8

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Abstract

Background

Methods

Results

Conclusion

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