Inhibition of Tumor Growth by Mouse Ror1 Specific Antibody in a Syngeneic Mouse Tumor Model Publisher Pubmed



Hassannia H¹ ; Amiri MM¹ ; Jadidiniaragh F² ; Hosseinighatar R¹ ; Khoshnoodi J¹ ; Sharifian RA³ ; Golsazshirazi F¹ ; Jedditehrani M⁴ ; Shokri F^{1, 4} Show Affiliations
Source: Immunology Letters Published:2018

Abstract

Introduction Immunotherapy with tumor-associated antigens (TAAs) is a potentially powerful approach to eradicate tumor cells. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) plays a crucial role for survival of tumor cells and is overexpressed in various malignancies. In the present study, we developed a syngeneic mouse tumor model to assess anti-tumor effect of mouse ROR1 specific polyclonal antibody (pAb) in vivo. Materials and methods Mouse ROR1 specific antibody was produced in rabbit using recombinant ROR1 protein. Tow mouse tumor cell lines, (4T1 and CT26), were transfected with full length mouse ROR1 construct and stable clones were selected and characterized by immunocytochemistry, Western blot and flow cytometry. In vitro and in vivo anti-tumor activities of anti-ROR1 antibody were assessed by XTT and syngeneic BALB/c mouse model, respectively. Results We successfully established two mouse ROR1-overexpressing tumor cell lines. The in vitro results indicate that the ROR1pAb did not significantly inhibit growth of ROR1+ cell lines. One of these cell lines (CT26-ROR1) was implanted in syngeneic BALB/c mice to assess anti-ROR1 tumor inhibitory activity in vivo. The tumor size was significantly reduced in mice treated with ROR1 specific pAb. Conclusion Our results demonstrated for the first time tumor inhibitory effect of mouse ROR1 specific antibody in a syngeneic mouse tumor model. This model is a promising tool for preclinical assessment of ROR1 therapeutics and investigation of the underling molecular mechanisms. © 2017 European Federation of Immunological Societies