A novel single-chain antibody redirects adenovirus to IL13Rα2-expressing brain tumors

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

doi:10.1038/srep18133

A novel single-chain antibody redirects adenovirus to IL13Rα2-expressing brain tumors

Julius W. Kim, Jacob S. Young, Elena Solomaha, Deepak Kanojia, Maciej S. Lesniak, Irina V. Balyasnikova^*

^*Corresponding author for this work

Neurological Surgery

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

The generation of a targeting agent that strictly binds to IL13Rα2 will significantly expand the therapeutic potential for the treatment of IL13Rα2-expressing cancers. In order to fulfill this goal, we generated a single-chain antibody (scFv47) from our parental IL13Rα2 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 IL13Rα2, but not to IL13Rα1 with a high affinity of 0.9 · 10^-9 M, similar to that of the parental antibody. Moreover, the scFv47 successfully redirects adenovirus to IL13Rα2 expressing glioma cells both in vitro and in vivo. Our data validate scFv47 as a highly selective IL13Rα2 targeting agent and justify further development of scFv47-modified oncolytic adenovirus and other therapeutics for the treatment of IL13Rα2-expressing glioma and other malignancies.

Original language	English (US)
Article number	18133
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep18133
State	Published - Dec 14 2015

Funding

Authors thank the Frank W. Fitch Monoclonal Antibody Facility of the University of Chicago for providing anti-c-myc monoclonal antibody (clone (9E10). We are also thankful to the Biophysics Core Facility of the University of Chicago for the valuable technical assistance and guidance provided for affinity studies. This work was supported in part by the National Institute of Health (1R21NS089802 and 5R01CA122930). JSY was supported in part by the NIH NIDDK grant #2T35DK062719-27 and the Neurosurgery Research and Education Foundation Medical Student Summer Research Fellowship.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "A novel single-chain antibody redirects adenovirus to IL13Rα2-expressing brain tumors",

abstract = "The generation of a targeting agent that strictly binds to IL13Rα2 will significantly expand the therapeutic potential for the treatment of IL13Rα2-expressing cancers. In order to fulfill this goal, we generated a single-chain antibody (scFv47) from our parental IL13Rα2 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 IL13Rα2, but not to IL13Rα1 with a high affinity of 0.9 · 10-9 M, similar to that of the parental antibody. Moreover, the scFv47 successfully redirects adenovirus to IL13Rα2 expressing glioma cells both in vitro and in vivo. Our data validate scFv47 as a highly selective IL13Rα2 targeting agent and justify further development of scFv47-modified oncolytic adenovirus and other therapeutics for the treatment of IL13Rα2-expressing glioma and other malignancies.",

author = "Kim, {Julius W.} and Young, {Jacob S.} and Elena Solomaha and Deepak Kanojia and Lesniak, {Maciej S.} and Balyasnikova, {Irina V.}",

note = "Funding Information: Authors thank the Frank W. Fitch Monoclonal Antibody Facility of the University of Chicago for providing anti-c-myc monoclonal antibody (clone (9E10). We are also thankful to the Biophysics Core Facility of the University of Chicago for the valuable technical assistance and guidance provided for affinity studies. This work was supported in part by the National Institute of Health (1R21NS089802 and 5R01CA122930). JSY was supported in part by the NIH NIDDK grant #2T35DK062719-27 and the Neurosurgery Research and Education Foundation Medical Student Summer Research Fellowship.",

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AU - Balyasnikova, Irina V.

N1 - Funding Information: Authors thank the Frank W. Fitch Monoclonal Antibody Facility of the University of Chicago for providing anti-c-myc monoclonal antibody (clone (9E10). We are also thankful to the Biophysics Core Facility of the University of Chicago for the valuable technical assistance and guidance provided for affinity studies. This work was supported in part by the National Institute of Health (1R21NS089802 and 5R01CA122930). JSY was supported in part by the NIH NIDDK grant #2T35DK062719-27 and the Neurosurgery Research and Education Foundation Medical Student Summer Research Fellowship.

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N2 - The generation of a targeting agent that strictly binds to IL13Rα2 will significantly expand the therapeutic potential for the treatment of IL13Rα2-expressing cancers. In order to fulfill this goal, we generated a single-chain antibody (scFv47) from our parental IL13Rα2 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 IL13Rα2, but not to IL13Rα1 with a high affinity of 0.9 · 10-9 M, similar to that of the parental antibody. Moreover, the scFv47 successfully redirects adenovirus to IL13Rα2 expressing glioma cells both in vitro and in vivo. Our data validate scFv47 as a highly selective IL13Rα2 targeting agent and justify further development of scFv47-modified oncolytic adenovirus and other therapeutics for the treatment of IL13Rα2-expressing glioma and other malignancies.

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A novel single-chain antibody redirects adenovirus to IL13Rα2-expressing brain tumors

Abstract

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UN SDGs

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