Abstract
Osteosarcoma (OS) represents 3.4% of all childhood cancers with overall survival of 70% not improving in 30 years. The consistent surface overexpression of insulin-like growth factor-2 receptor (IGF2R) has been reported in commercial and patient-derived xenograft (PDX) OS cell lines. We aimed to assess efficacy and safety of treating PDX and commercial OS tumors in mice with radiolabeled antibody to IGF2R and to investigate IGF2R expression on canine OS tumors. IGF2R expression on human commercial lines 143B and SaOS2 and PDX lines OS-17, OS-33 and OS-31 was evaluated by FACS. The biodistribution and microSPECT/CT imaging with 111Indium-2G11 mAb was performed in 143B and OS-17 tumor-bearing SCID mice and followed by radioimmunotherapy (RIT) with 177Lutetium-2G11 and safety evaluation. IGF2R expression in randomly selected canine OS tumors was measured by immunohistochemistry. All OS cell lines expressed IGF2R. Biodistribution and microSPECT/CT revealed selective uptake of 2G11 mAb in 143B and OS-17 xenografts. RIT significantly slowed down the growth of OS-17 and 143B tumors without local and systemic toxicity. Canine OS tumors expressed IGF2R. This study demonstrates the feasibility of targeting IGF2R on OS in PDX and spontaneous canine tumors and sets the stage for further development of RIT of OS using comparative oncology.
Highlights
STAININGISOTYPE CONTROL ANTIBODY – MOPC-21insulin-like growth factor-2 receptor (IGF2R) SPECIFIC ANTIBODY – 2G11 f) *osteosarcoma risk[8]
OS cell lines expressed various levels of IGF2R accompanied by internalization of the monoclonal antibody (mAb) to IGF2R. 2G11 mAb binds to IGF2R-expressing cell lines and preserves its immunoreactivity post-conjugation of the bifunctional chelating agent
We first sought to establish if 2G11 mAb to human and murine IGF2R would bind to OS across multiple cell lines
Summary
STAININGISOTYPE CONTROL ANTIBODY – MOPC-21IGF2R SPECIFIC ANTIBODY – 2G11 f) *osteosarcoma risk[8]. Targeted radionuclide therapy (TRT) delivers cytocidal radiation in the form of alpha- or beta-particle emitting radionuclides to the tumor with high precision, avoiding many of the side effects associated with external beam radiation therapy (EBRT). Radioimmunotherapy (RIT) is a subset of TRT and is a method of delivering cytotoxic radiation in a targeted fashion whereby an antigen-specific antibody is bound to either an alpha- or beta-emitting radioisotope[9,10]. RIT delivers cytocidal radiation to the targeted cells independently of any specific pathway and is unaffected by resistance mechanisms or tumor microenvironmental fluctuations. It permits for systemic administration, antibody-mediated specificity, and physical cytocidal damage in a manner well tolerated by the patient
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