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Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program.

Publication ,  Journal Article
Kolb, EA; Gorlick, R; Houghton, PJ; Morton, CL; Lock, R; Carol, H; Reynolds, CP; Maris, JM; Keir, ST; Billups, CA; Smith, MA
Published in: Pediatr Blood Cancer
June 2008

BACKGROUND: SCH 717454 (19D12) is a fully human antibody directed against the insulin-like growth factor 1 receptor (IGF-1R), which is implicated in the growth and metastatic phenotype of a broad range of malignancies. The activity of SCH 717454 was evaluated against the in vitro and in vivo panels of the Pediatric Preclinical Testing Program (PPTP). PROCEDURES: SCH 717454 was tested against the PPTP in vitro panel at concentrations ranging from 0.01 to 100 nM and was tested against the PPTP in vivo panel at a dose of 0.5 mg per mouse administered twice weekly for 4 weeks via intraperitoneal injection. RESULTS: SCH 717454 was ineffective at retarding growth of cell lines in the in vitro panel. In vivo, SCH 717454 significantly increased event-free survival in 20 of 35 (57%) solid tumor xenograft models with tumor regressions in one Ewing sarcoma model (complete response) and 2 osteosarcoma models (maintained complete responses). Using the time to event activity measure, SCH 717454 had intermediate (n = 9) or high (n = 1) activity against 31 evaluable solid tumor xenografts, including xenografts from the rhabdoid tumor, Ewing, rhabdomyosarcoma, glioblastoma, neuroblastoma, and osteosarcoma panels. SCH 717454 showed little activity against the 8 xenografts of the acute lymphoblastic leukemia panel. CONCLUSIONS: SCH 717454 demonstrated broad antitumor activity against the PPTP's in vivo solid tumor panels. Further characterization of the molecular predictors of response and of the activity of combinations of SCH 717454 with other anticancer agents are anticipated.

Duke Scholars

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Published In

Pediatr Blood Cancer

DOI

EISSN

1545-5017

Publication Date

June 2008

Volume

50

Issue

6

Start / End Page

1190 / 1197

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Receptor, IGF Type 1
  • Oncology & Carcinogenesis
  • Mice, Inbred Strains
  • Mice
  • Humans
  • Female
  • Child
  • Cells, Cultured
  • Cell Proliferation
 

Citation

APA
Chicago
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MLA
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Kolb, E. A., Gorlick, R., Houghton, P. J., Morton, C. L., Lock, R., Carol, H., … Smith, M. A. (2008). Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program. Pediatr Blood Cancer, 50(6), 1190–1197. https://doi.org/10.1002/pbc.21450
Kolb, E Anders, Richard Gorlick, Peter J. Houghton, Christopher L. Morton, Richard Lock, Hernan Carol, C Patrick Reynolds, et al. “Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program.Pediatr Blood Cancer 50, no. 6 (June 2008): 1190–97. https://doi.org/10.1002/pbc.21450.
Kolb EA, Gorlick R, Houghton PJ, Morton CL, Lock R, Carol H, et al. Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jun;50(6):1190–7.
Kolb, E. Anders, et al. “Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program.Pediatr Blood Cancer, vol. 50, no. 6, June 2008, pp. 1190–97. Pubmed, doi:10.1002/pbc.21450.
Kolb EA, Gorlick R, Houghton PJ, Morton CL, Lock R, Carol H, Reynolds CP, Maris JM, Keir ST, Billups CA, Smith MA. Initial testing (stage 1) of a monoclonal antibody (SCH 717454) against the IGF-1 receptor by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jun;50(6):1190–1197.
Journal cover image

Published In

Pediatr Blood Cancer

DOI

EISSN

1545-5017

Publication Date

June 2008

Volume

50

Issue

6

Start / End Page

1190 / 1197

Location

United States

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Receptor, IGF Type 1
  • Oncology & Carcinogenesis
  • Mice, Inbred Strains
  • Mice
  • Humans
  • Female
  • Child
  • Cells, Cultured
  • Cell Proliferation