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Characterization of novel neutralizing mouse monoclonal antibody JM1-24-3 developed against MUC18 in metastatic melanoma.
Feng, Runhua; Wang, Yuling; Ramachandran, Vijaya; Ma, Qinhong; May, Matthew M; Li, Ming; Zhou, Joe X; Xu, Xiang; Xu, Kejing; Fang, Shenying; Xia, Weiya; Sui, Dawen; Liu, Huey; Gao, Xiaolian; Prieto, Victor; Blacklow, Stephen C; Lu, Mason; Lee, Jeffrey E.
Affiliation
  • Feng R; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Wang Y; Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • Ramachandran V; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Ma Q; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • May MM; MedAbome, Inc., Fremont, CA, 94538, USA.
  • Li M; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Zhou JX; Department of Otolaryngology, Mayo School of Graduate Medical Education, Rochester, MN, 55905, USA.
  • Xu X; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Xu K; Department of Pathology, Anhui Province Hospital, Anhui Medical University, Hefei, Anhui, 230032, China.
  • Fang S; LC Sciences, LLC, Houston, TX, 77054, USA.
  • Xia W; Department of Biological Chemistry and Molecular Pharmacology, Harvard University School of Medicine, Boston, MA, 02115, USA.
  • Sui D; Department of Pathology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
  • Liu H; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Gao X; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Prieto V; Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Blacklow SC; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Lu M; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Lee JE; Department of Biology and Biochemistry, The University of Houston, Houston, TX, 77204, USA.
J Exp Clin Cancer Res ; 39(1): 273, 2020 Dec 05.
Article in En | MEDLINE | ID: mdl-33278894
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Melanoma / Antibodies, Monoclonal Type of study: Clinical_trials Limits: Animals / Humans / Male Language: En Journal: J Exp Clin Cancer Res Year: 2020 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Melanoma / Antibodies, Monoclonal Type of study: Clinical_trials Limits: Animals / Humans / Male Language: En Journal: J Exp Clin Cancer Res Year: 2020 Type: Article Affiliation country: United States