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Detection and targeting insulin growth factor receptor type 2 (IGF2R) in osteosarcoma PDX in mouse models and in

Sharayu Karkare1, Kevin J H Allen1, Rubin Jiao1

  • 1University of Saskatchewan, Saskatoon, Canada.

Scientific Reports
|August 9, 2019
PubMed

Insights

Targeting insulin-like growth factor-2 receptor (IGF2R) with radiolabeled antibodies shows promise for osteosarcoma (OS) treatment. This approach effectively slowed tumor growth in preclinical models with no observed toxicity.

Area of Science:

  • Oncology
  • Immunotherapy
  • Radiopharmaceuticals

Background:

  • Osteosarcoma (OS) is a rare childhood cancer with stagnant survival rates.
  • Insulin-like growth factor-2 receptor (IGF2R) is consistently overexpressed on OS cells.

Purpose of the Study:

  • To evaluate the efficacy and safety of radioimmunotherapy (RIT) targeting IGF2R in OS models.
  • To investigate IGF2R expression in canine OS for comparative oncology.

Main Methods:

  • Assessed IGF2R expression using Flow Cytometry (FACS) and immunohistochemistry.
  • Performed biodistribution and microSPECT/CT imaging with 111Indium-2G11 mAb.
  • Conducted RIT with 177Lutetium-2G11 in human OS xenografts in mice.

Main Results:

  • All tested human and canine OS samples expressed IGF2R.
  • The 2G11 mAb showed selective uptake in human OS xenografts.
  • RIT significantly inhibited tumor growth in mice without causing local or systemic toxicity.

Conclusions:

  • Targeting IGF2R is a feasible strategy for OS treatment.
  • RIT with 177Lutetium-2G11 demonstrates therapeutic potential for OS.
  • The study supports the use of comparative oncology, including canine models, for OS RIT development.

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