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Updated: Jan 29, 2026
Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
Published on: April 11, 2018
Investigating a chimeric anti-mouse PDGFRα antibody as a radiosensitizer in primary mouse sarcomas
Erin J Song1, Kathleen A Ashcraft1, Caitlin D Lowery2
1Department of Radiation Oncology, Duke University School of Medicine, Durham, NC 27710, United States.
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.
Insights
The chimeric anti-mouse PDGFRα antibody 1E10Fc did not enhance radiation therapy (RT) in a primary soft tissue sarcoma (STS) mouse model. Further research is needed to explore PDGFRα-targeted therapies in combination with RT for STS treatment.
Area of Science:
- Oncology
- Immunotherapy
- Radiation Oncology
Background:
- Olaratumab, a monoclonal antibody targeting platelet-derived growth factor receptor alpha (PDGFRα), has shown promise in advanced soft tissue sarcoma (STS).
- Radiation therapy (RT) is a standard treatment for high-risk localized STS, but its combination with olaratumab has not been evaluated.
- This study investigates the potential of a chimeric anti-mouse PDGFRα antibody (1E10Fc) as a radiosensitizer in a preclinical STS model.
Purpose of the Study:
- To evaluate the efficacy of 1E10Fc as a radiosensitizer when combined with RT in a primary mouse model of STS.
- To assess the impact of 1E10Fc and RT on tumor growth, microvessel density, and micrometastasis formation.
Main Methods:
- Primary STS were established in mice and treated with either isotype control or 1E10Fc, with or without concurrent RT (25 Gy in 5 fractions).
- Tumor growth was monitored, and upon reaching a specified size, tumors and lungs were harvested for analysis.
- Microvessel density was assessed via CD31 staining, and PDGFRα expression was evaluated. Lung micrometastases were quantified.
Main Results:
- RT significantly delayed tumor growth, but 1E10Fc did not enhance this effect, irrespective of RT combination.
- The combination of 1E10Fc and RT led to reduced microvessel density in primary tumors.
- A trend towards fewer lung micrometastases was observed in the 1E10Fc + RT group, but this did not reach statistical significance.
Conclusions:
- The chimeric anti-mouse PDGFRα antibody 1E10Fc did not demonstrate radiosensitizing effects in this primary STS mouse model.
- Further investigation into PDGFRα-targeted agents and their combination with RT in STS is warranted, potentially exploring different antibodies or treatment schedules.
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