title: Inhibition of metastasis of rhabdomyosarcoma by a novel neutralizing antibody to CXC chemokine receptor-4.
abstract: Rhabdomyosarcoma is the most common soft tissue sarcoma affecting children, and the overall cure rate of children with metastatic disease remains below 30%. The CXC chemokine receptor-4 (CXCR4)/stromal cell-derived factor-1 (SDF1) axis has been implicated in the promotion of metastatic potential in several tumors. In this study, we developed a novel anti-CXCR4 mAb, CF172, and investigated its antimetastatic activity against rhabdomyosarcoma cells in vitro and in vivo, to evaluate its potential as a therapeutic antibody to treat rhabdomyosarcoma. The CF172 molecule showed a specific binding reactivity against human CXCR4, as well as a specific neutralizing activity against CXCR4/SDF1 signal transduction. Using CF172, we determined that SJCRH30 rhabdomyosarcoma cells expressed high levels of CXCR4. In addition, CF172 was found to inhibit the SDF1-induced migration activity of SJCRH30 cells in vitro. Using xenograft models of SJCRH30 cells, we carried out in vivo efficacy studies for peritoneal and lymph node metastasis, which were clinically observed in rhabdomyosarcoma. These studies indicated that CF172 significantly decreased both types of metastasis of SJCRH30. In conclusion, we found that a novel anti-CXCR4 mAb, CF172, with specific reactivity against human CXCR4, prevented peritoneal metastasis and lymph node metastasis of rhabdomyosarcoma in animal models. These results suggest that CF172 is a potential antimetastasis therapeutic antibody for rhabdomyosarcoma treatment.
authors.affiliation: Research Division, Chugai Pharmaceutical Co. Ltd., Kanagawa, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kashima
authors.forename: Miho
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Sato
authors.forename: Junichi
authors.initials: J
authors.lastname: Hata
authors.forename: Nobuya
authors.initials: N
authors.lastname: Ishii
authors.forename: Yuko
authors.initials: Y
authors.lastname: Aoki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D000080908:Broadly Neutralizing Antibodies; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D010534:Peritoneal Neoplasms / Q000556:secondary; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000556:secondary
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; C000593700:CF172 antibody; D019718:Receptors, CXCR4
keywords: CXCR4 Receptors; Monoclonal Antibodies; Neoplasm Metastasis; Neutralizing Antibodies; Rhabdomyosarcoma