Investigating a chimeric anti-mouse PDGFRα antibody as a radiosensitizer in primary mouse sarcomas.

Published

Journal Article

BACKGROUND: Olaratumab (LY3012207/IMC-3G3/Lartruvo™) is a fully human monoclonal antibody specific for platelet-derived growth factor receptor alpha (PDGFRα). Phase Ib/II trial results of olaratumab plus doxorubicin in adult patients with advanced soft tissue sarcoma (STS) supported accelerated FDA approval of this regimen. Radiation therapy (RT) is frequently used for high-risk localized STS. However, olaratumab has not been tested with concurrent RT. Here, we evaluate the chimeric anti-mouse PDGFRα antibody 1E10Fc as a radiosensitizer in a primary mouse model of STS. METHODS: Primary STS were initiated in mice. When tumors reached 70 mm3, mice were allocated into treatment groups: 1) isotype, 2) 1E10Fc, 3) isotype + RT, 4) 1E10Fc + RT. 1E10Fc or isotype was given biweekly. RT (25 Gy delivered in 5 daily 5 Gy fractions) was initiated on Day 0 with first drug treatment. Tumors were measured 3× per week. Upon reaching 900 mm3, tumors and lungs were harvested. A two-way ANOVA was performed to compare tumor growth delay. Primary tumors were stained for CD31 and PDGFRα and lungs were assessed for micrometastases. A Chi-square test was performed to compare the development of micrometastases in the lungs after treatment with 1E10Fc or isotype. FINDINGS: RT significantly delayed time to tumor quintupling compared to no RT (p < 0·0001) [two-way ANOVA], but no difference in tumor growth was seen between mice receiving isotype or 1E10Fc treatment regardless of concurrent RT. Lower microvessel density was observed in the 1E10Fc + RT group. Fewer mice treated with 1E10Fc had micrometastases, but this difference was not statistically significant (p < 0·09). INTERPRETATION: 1E10Fc did not act as a radiosensitizer in this primary STS model. FUNDING: This study was funded by a research agreement from Eli Lilly and Company.

Full Text

Duke Authors

Cited Authors

  • Song, EJ; Ashcraft, KA; Lowery, CD; Mowery, YM; Luo, L; Ma, Y; Campos, LDS; Cardona, DM; Stancato, L; Kirsch, DG

Published Date

  • February 2019

Published In

Volume / Issue

  • 40 /

Start / End Page

  • 224 - 230

PubMed ID

  • 30711517

Pubmed Central ID

  • 30711517

Electronic International Standard Serial Number (EISSN)

  • 2352-3964

Digital Object Identifier (DOI)

  • 10.1016/j.ebiom.2019.01.046

Language

  • eng

Conference Location

  • Netherlands