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Identification of CD73 as the antigen of an antigen-unknown monoclonal antibody established by exosome immunization, and its antibody-drug conjugate exerts an antitumor effect on glioblastoma cell lines

View ORCID ProfileTakahiro anzai, Shinji Saijou, Hiroki Takashima, Misato Hara, Shingo Hanaoka, Yasuhiro Matsumura, Masahiro Yasunaga
doi: https://doi.org/10.1101/2021.09.30.462527
Takahiro anzai
1Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan
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  • ORCID record for Takahiro anzai
Shinji Saijou
1Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan
2Research division, RIN Institute, Inc., 2-5-10, Shintomi, Chuo-ku, Tokyo, 104-0041, Japan
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Hiroki Takashima
1Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan
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Misato Hara
3Tamagawa Seiki Co., Ltd, 1879, Ohyasumi, Iida, Nagano, 395-8515, Japan
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Shingo Hanaoka
1Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan
2Research division, RIN Institute, Inc., 2-5-10, Shintomi, Chuo-ku, Tokyo, 104-0041, Japan
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Yasuhiro Matsumura
1Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan
2Research division, RIN Institute, Inc., 2-5-10, Shintomi, Chuo-ku, Tokyo, 104-0041, Japan
4Department of Immune Medicine, National Cancer Center Research Institute, National Cancer Center, 5-1-1, Tsukiji, Chuo-Ku, Tokyo 104-0045, Japan
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Masahiro Yasunaga
1Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan
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  • For correspondence: mayasuna@east.ncc.go.jp
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Abstract

Development of antibodies against the native structure of membrane proteins with multiple transmembrane domains is challenging because it is difficult to prepare antigens with native structures. Previously, we successfully developed a monoclonal antibody against multi-pass membrane protein TMEM180 by exosome immunization in rats. This approach yielded antibod-ies that recognized cancer-specific antigens on the exosome. In this study, we performed im-munoprecipitation using magnetic beads to identify the antigen of one of the rat antibody clones, 0614, as CD73. We then converted antibody 0614 to human chimeric antibody 0614-5 and found that the humanized antibody did not inhibit CD73 enzymatic activity. Glioblastoma (GB) was the cancer type with the highest expression of CD73 in the tumor relative to healthy tissue. An antibody–drug conjugate (ADC) of 0614-5 exerted an antitumor effect on GB cell lines according to expression of CD73. The 0614-5-ADC could be used to treat cancers with high CD73 expression. In addition, our strategy could be used to determine the antigen of any antibody produced by exosome immunization.

Competing Interest Statement

Y.M. is co-founder, shareholder, and Board Member of RIN Institute, Inc. S.S. and S.H. are em-ployees of RIN Institute, Inc. M.H. is an employee of Tamagawa Seiki Co. Ltd. M.Y. is a share-holder of RIN Institute, Inc. The other authors declare no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted October 01, 2021.
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Identification of CD73 as the antigen of an antigen-unknown monoclonal antibody established by exosome immunization, and its antibody-drug conjugate exerts an antitumor effect on glioblastoma cell lines
Takahiro anzai, Shinji Saijou, Hiroki Takashima, Misato Hara, Shingo Hanaoka, Yasuhiro Matsumura, Masahiro Yasunaga
bioRxiv 2021.09.30.462527; doi: https://doi.org/10.1101/2021.09.30.462527
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Identification of CD73 as the antigen of an antigen-unknown monoclonal antibody established by exosome immunization, and its antibody-drug conjugate exerts an antitumor effect on glioblastoma cell lines
Takahiro anzai, Shinji Saijou, Hiroki Takashima, Misato Hara, Shingo Hanaoka, Yasuhiro Matsumura, Masahiro Yasunaga
bioRxiv 2021.09.30.462527; doi: https://doi.org/10.1101/2021.09.30.462527

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