A novel single-chain antibody redirects adenovirus to IL13R alpha 2-expressing brain tumors

作者：Kim Julius W; Young Jacob S; Solomaha Elena; Kanojia Deepak; Lesniak Maciej S; Balyasnikova Irina V

来源：Scientific Reports, 2015, 5: 18133.

DOI：10.1038/srep18133

The generation of a targeting agent that strictly binds to IL13R alpha 2 will significantly expand the therapeutic potential for the treatment of IL13R alpha 2-expressing cancers. In order to fulfill this goal, we generated a single-chain antibody (scFv47) from our parental IL13R alpha 2 monoclonal antibody and tested its binding properties. Furthermore, to demonstrate the potential therapeutic applicability of scFv47, we engineered an adenovirus by incorporating scFv47 as the targeting moiety in the viral fiber and characterized its properties in vitro and in vivo. The scFv47 binds to human recombinant IL13R alpha 2, but not to IL13R alpha 1 with a high affinity of 0.9.10(-9) M, similar to that of the parental antibody. Moreover, the scFv47 successfully redirects adenovirus to IL13R alpha 2 expressing glioma cells both in vitro and in vivo. Our data validate scFv47 as a highly selective IL13R alpha 2 targeting agent and justify further development of scFv47-modified oncolytic adenovirus and other therapeutics for the treatment of IL13R alpha 2-expressing glioma and other malignancies.

• 出版日期2015-12-14
• 单位西北大学