Development of Human Recombinant Antibodies Against ROR۱ Tumor Antigen

Background: Receptor tyrosine kinase-like orphan receptor ۱ (ROR۱) is an oncofetal antigen expressed on many types of cancer cells, but not normal adult cells. ROR۱ antigen contributes to cancer development and progression by several signaling pathways. ROR۱ expression has been associated with tumor growth, survival, and metastasis. In this study specific human recombinant antibodies were selected against ROR۱ antigen for their use in cancer immunotherapy. Methods: Phage display technology was used to produce phage antibody from a human scFv library. Phage concentration was determined to confirm the phage rescue process. Panning procedure was performed to isolate specific scFv clones against ROR۱ epitope. Phage ELISA was done to evaluate the reactivity of the selected scFvs. Results: Two specific human scFvs with frequencies of ۲۰% and ۲۵% were selected against ROR۱ peptide. The antibodies showed specific reaction to the corresponding epitopes in phage ELISA.  Conclusions: Cancer targeted therapy using human specific antibodies is a new strategy, which is used in cancer therapy. The selected specific scFvs that target ROR۱ epitope are human antibodies that originated from a human library and have the potential to be used in clinic in cancer immunotherapy of ROR۱ positive tumors without induction of human anti mouse antibody (HAMA) response.

Keywords:

ROR۱ , Phage display , scFV library , Cancer.