Abstract 5797: Impact of baseline tumor size on response to anti-CD47 immunotherapy in an osteosarcoma mouse model

Abstract Background and Purpose. Activation of tumor-associated macrophages (TAMs) by CD47 mAb therapy can be monitored with ferumoxytol-enhanced magnetic resonance imaging (MRI). The purpose of our study was to investigate if tumor size at baseline affects TAM response to CD47 mAb, as measured with ferumoxytol-MRI. Methods. Thirty female NOD scid gamma (NSG) mice with small-sized (tumor volume = 30 mm3), medium-sized (tumor volume = 500 mm3), and large (tumor volume = 1200 mm3) 143B osteosarcoma xenografts were treated with human CD47 mAb (10 mg/kg, day 1, 3, and 5 for 1 week) or PBS (control group). All mice underwent MRI scans at baseline and at one week after CD47 mAb or sham treatment. Post-treatment scans were obtained before and after intravenous infusion of ferumoxytol nanoparticles (30 Fe mg/kg). We measured tumor T2* relaxation times as a quantitive measure of nanoparticle retention in TAM. The tumor ferumoxytol enhancement, calculated as: ΔT2* = 100 * (T2*precontrast - T2*postcontrast) / T2*precontrast, was compared between experimental groups using exact two-sided Wilcoxon rank-sum tests. Histology served as standard of reference. Results. At baseline, tumors of CD47 mAb and PBS-treated mice demonstrated no significant difference in T2* relaxation time, regardless of tumor size (all p>0.05). After CD47 mAb therapy, tumors treated with CD47 mAb demonstrated significantly shorter T2* relaxation times compared to PBS-treated mice (all p<0.001). The tumor T2* enhancement was significantly higher in small tumors (ΔT2* = 41.3% +/- 2.182%) compared to large tumors (ΔT2* = 2.93% +/- 2.474%; p=0.001), indicating stronger nanoparticle phagocytosis in small sized tumors, apparently due to increased TAM activation. There was not statistically significance difference between T2* relaxation time of small and medium-sized tumors in all time points (all p> 0.05). Histopathological correlations confirmed a significantly higher number of CD80-positive TAMs in small sized tumors after CD47 mAb therapy (61.28% +/- 1.77%) compared to large sized tumors (3.38% +/- 0.81%, p<0.001). Conclusion. Tumor size at baseline affects TAM response to CD47 mAb. Smaller osteosarcomas exhibit a more pronounced TAM response to CD47 mAb therapy compared to larger tumors. Citation Format: Raheleh Roudi, Iryna Vasylkiv, Laura Pisani, Tie Liang, Raya Saab, Heike Daldrup-Link. Impact of baseline tumor size on response to anti-CD47 immunotherapy in an osteosarcoma mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5797.