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

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

doi:10.1186/s13046-020-01722-8

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

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

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English (US)
Article number	273
Journal	Journal of Experimental and Clinical Cancer Research
Volume	39
Issue number	1
DOIs	https://doi.org/10.1186/s13046-020-01722-8
State	Published - Dec 2020

Keywords

CD146
MUC18
Metastatic melanoma
Targeted therapy
Therapeutic antibody

ASJC Scopus subject areas

Oncology
Cancer Research

MD Anderson CCSG core facilities

Biostatistics Resource Group
Tissue Biospecimen and Pathology Resource
Bioinformatics Shared Resource
Functional Proteomics Reverse Phase Protein Array Core

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10.1186/s13046-020-01722-8

Cite this

Feng, R., Wang, Y., Ramachandran, V., Ma, Q., May, M. M., Li, M., Zhou, J. X., Xu, X., Xu, K., Fang, S., Xia, W., Sui, D., Liu, H., Gao, X., Prieto, V., Blacklow, S. C., Lu, M., & Lee, J. E. (2020). Characterization of novel neutralizing mouse monoclonal antibody JM1-24-3 developed against MUC18 in metastatic melanoma. Journal of Experimental and Clinical Cancer Research, 39(1), Article 273. https://doi.org/10.1186/s13046-020-01722-8

Feng, R, Wang, Y, Ramachandran, V, Ma, Q, May, MM, Li, M, Zhou, JX, Xu, X, Xu, K, Fang, S, Xia, W, Sui, D, Liu, H, Gao, X, Prieto, V, Blacklow, SC, Lu, M & Lee, JE 2020, 'Characterization of novel neutralizing mouse monoclonal antibody JM1-24-3 developed against MUC18 in metastatic melanoma', Journal of Experimental and Clinical Cancer Research, vol. 39, no. 1, 273. https://doi.org/10.1186/s13046-020-01722-8

@article{2e968c9783c24f29b9639cffd6e16e78,

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

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.",

keywords = "CD146, MUC18, Metastatic melanoma, Targeted therapy, Therapeutic antibody",

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

note = "Funding Information: This work was supported by the NCI/NIH SPORE grant P50 CA093459 and the UTMDACC Support Grant P30 CA016672 (Clinical Trials Support Resource); philanthropic contributions to UTMDACC Moon Shots Program; UTMDACC Various Donors Melanoma and Skin Cancers Priority Program Fund; Miriam and Jim Mulva Research Fund; McCarthy Skin Cancer Research Fund and Marit Peterson Fund for Melanoma Research. Funding Information: We thank Z.G. Zhu and B.Y. Liu (Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China) for BGC823 and MKN45 cell lines. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

doi = "10.1186/s13046-020-01722-8",

language = "English (US)",

volume = "39",

journal = "Journal of Experimental and Clinical Cancer Research",

issn = "0392-9078",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Characterization of novel neutralizing mouse monoclonal antibody JM1-24-3 developed against MUC18 in metastatic melanoma

AU - Feng, Runhua

AU - Wang, Yuling

AU - Ramachandran, Vijaya

AU - Ma, Qinhong

AU - May, Matthew M.

AU - Li, Ming

AU - Zhou, Joe X.

AU - Xu, Xiang

AU - Xu, Kejing

AU - Fang, Shenying

AU - Xia, Weiya

AU - Sui, Dawen

AU - Liu, Huey

AU - Gao, Xiaolian

AU - Prieto, Victor

AU - Blacklow, Stephen C.

AU - Lu, Mason

AU - Lee, Jeffrey E.

N1 - Funding Information: This work was supported by the NCI/NIH SPORE grant P50 CA093459 and the UTMDACC Support Grant P30 CA016672 (Clinical Trials Support Resource); philanthropic contributions to UTMDACC Moon Shots Program; UTMDACC Various Donors Melanoma and Skin Cancers Priority Program Fund; Miriam and Jim Mulva Research Fund; McCarthy Skin Cancer Research Fund and Marit Peterson Fund for Melanoma Research. Funding Information: We thank Z.G. Zhu and B.Y. Liu (Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China) for BGC823 and MKN45 cell lines. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12

Y1 - 2020/12

N2 - 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.

AB - 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.

KW - CD146

KW - MUC18

KW - Metastatic melanoma

KW - Targeted therapy

KW - Therapeutic antibody

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U2 - 10.1186/s13046-020-01722-8

DO - 10.1186/s13046-020-01722-8

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AN - SCOPUS:85097105958

SN - 0392-9078

VL - 39

JO - Journal of Experimental and Clinical Cancer Research

JF - Journal of Experimental and Clinical Cancer Research

IS - 1

M1 - 273

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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