Targeted therapy of osteosarcoma with radiolabeled monoclonal antibody to an insulin-like growth factor-2 receptor (IGF2R)

Introduction Osteosarcoma overall survival has plateaued around 70%, without meaningful improvements in over 30 years. Outcomes for patients with overt metastatic disease at presentation or who relapse are dismal. In this study we investigated a novel osteosarcoma therapy utilizing radioimmunotherapy (RIT) targeted to IGF2R, which is widely expressed in OS. Methods Binding efficiency of the Rhenium-188(¹⁸⁸Re)-labeled IGF2R-specific monoclonal antibody (mAb) to IGF2R on OS17 OS cells was assessed with Scatchard plot analysis. Biodistribution studies were performed in heterotopic murine osteosarcoma xenografts. Tumor growth was compared over a 24-day period post-treatment between mice randomized to receive ¹⁸⁸Re-labeled IGF2R-specific murine mAb MEM-238 (¹⁸⁸Re-MEM-238) or one of three controls: ¹⁸⁸Re-labeled isotype control mAb, unlabeled MEM-238, or no treatment. Results Results demonstrate that the radioimmunoconjugate had a high binding constant to IGF2R. Both ¹⁸⁸Re-MEM-238 and the isotype control had similar initial distribution in normal tissue. After 48 h ¹⁸⁸Re-MEM-238 exhibited a 1.8 fold selective uptake within tumor compared to the isotype control (p = 0.057). Over 24 days, the tumor growth ratio was suppressed in animals treated with RIT compared to unlabeled and untreated controls (p = 0.005) as demonstrated by a 38% reduction of IGF2R expressing osteosarcoma cells in the RIT group (p = 0.002). Conclusions In conclusion, given the lack of new effective therapies in osteosarcoma, additional investigation into this target is warranted. Advances in knowledge High expression of IGF2R on osteosarcoma tumors, paired with the specificity and in vivo anti-cancer activity of ¹⁸⁸Re-labeled IGF2R-specific mAb suggests that IGF2R may represent a novel therapeutic target in the treatment of osteosarcoma. Implications for patient care This targeted approach offers the benefits of being independent of a specific pathway, a resistance mechanism, and/or an inherent biologic tumor trait and therefore is relevant to all OS tumors that express IGF2R.