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Article

In Vitro Tumor Cell-Binding Assay to Select High-Binding Antibody and Predict Therapy Response for Personalized 64Cu-Intraperitoneal Radioimmunotherapy against Peritoneal Dissemination of Pancreatic Cancer: A Feasibility Study

by
Fukiko Hihara
1,
Hiroki Matsumoto
1,2,
Mitsuyoshi Yoshimoto
3,
Takashi Masuko
4,
Yuichi Endo
4,
Chika Igarashi
1,
Tomoko Tachibana
1,
Mitsuhiro Shinada
1,5,
Ming-Rong Zhang
1,
Gene Kurosawa
6,
Aya Sugyo
1,
Atsushi B. Tsuji
1,
Tatsuya Higashi
1,
Hiroaki Kurihara
2,
Makoto Ueno
7 and
Yukie Yoshii
1,2,*
1
Department of Molecular Imaging and Theranostics, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
2
Department of Diagnostic Radiology, Kanagawa Cancer Center, Kanagawa 241-8515, Japan
3
Division of Functional Imaging, National Cancer Center Hospital East, Chiba 277-8577, Japan
4
School of Pharmacy, Kindai University, Osaka 577-8502, Japan
5
Faculty of Science, Toho University, Chiba 274-8510, Japan
6
International Center for Cell and Gene Therapy, Fujita Health University, Aichi 470-1192, Japan
7
Department of Gastroenterology, Kanagawa Cancer Center, Kanagawa 241-8515, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(10), 5807; https://doi.org/10.3390/ijms23105807
Submission received: 20 April 2022 / Revised: 12 May 2022 / Accepted: 19 May 2022 / Published: 22 May 2022
(This article belongs to the Section Molecular Biology)
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Abstract

Peritoneal dissemination of pancreatic cancer has a poor prognosis. We have reported that intraperitoneal radioimmunotherapy using a 64Cu-labeled antibody (64Cu-ipRIT) is a promising adjuvant therapy option to prevent this complication. To achieve personalized 64Cu-ipRIT, we developed a new in vitro tumor cell-binding assay (64Cu-TuBA) system with a panel containing nine candidate 64Cu-labeled antibodies targeting seven antigens (EGFR, HER2, HER3, TfR, EpCAM, LAT1, and CD98), which are reportedly overexpressed in patients with pancreatic cancer. We investigated the feasibility of 64Cu-TuBA to select the highest-binding antibody for individual cancer cell lines and predict the treatment response in vivo for 64Cu-ipRIT. 64Cu-TuBA was performed using six human pancreatic cancer cell lines. For three cell lines, an in vivo treatment study was performed with 64Cu-ipRIT using high-, middle-, or low-binding antibodies in each peritoneal dissemination mouse model. The high-binding antibodies significantly prolonged survival in each mouse model, while low-and middle-binding antibodies were ineffective. There was a correlation between in vitro cell binding and in vivo therapeutic efficacy. Our findings suggest that 64Cu-TuBA can be used for patient selection to enable personalized 64Cu-ipRIT. Tumor cells isolated from surgically resected tumor tissues would be suitable for analysis with the 64Cu-TuBA system in future clinical studies.
Keywords: 64Cu-intraperitoneal radioimmunotherapy; in vitro tumor cell-binding assay; pancreatic cancer; peritoneal dissemination 64Cu-intraperitoneal radioimmunotherapy; in vitro tumor cell-binding assay; pancreatic cancer; peritoneal dissemination

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MDPI and ACS Style

Hihara, F.; Matsumoto, H.; Yoshimoto, M.; Masuko, T.; Endo, Y.; Igarashi, C.; Tachibana, T.; Shinada, M.; Zhang, M.-R.; Kurosawa, G.; et al. In Vitro Tumor Cell-Binding Assay to Select High-Binding Antibody and Predict Therapy Response for Personalized 64Cu-Intraperitoneal Radioimmunotherapy against Peritoneal Dissemination of Pancreatic Cancer: A Feasibility Study. Int. J. Mol. Sci. 2022, 23, 5807. https://doi.org/10.3390/ijms23105807

AMA Style

Hihara F, Matsumoto H, Yoshimoto M, Masuko T, Endo Y, Igarashi C, Tachibana T, Shinada M, Zhang M-R, Kurosawa G, et al. In Vitro Tumor Cell-Binding Assay to Select High-Binding Antibody and Predict Therapy Response for Personalized 64Cu-Intraperitoneal Radioimmunotherapy against Peritoneal Dissemination of Pancreatic Cancer: A Feasibility Study. International Journal of Molecular Sciences. 2022; 23(10):5807. https://doi.org/10.3390/ijms23105807

Chicago/Turabian Style

Hihara, Fukiko, Hiroki Matsumoto, Mitsuyoshi Yoshimoto, Takashi Masuko, Yuichi Endo, Chika Igarashi, Tomoko Tachibana, Mitsuhiro Shinada, Ming-Rong Zhang, Gene Kurosawa, and et al. 2022. "In Vitro Tumor Cell-Binding Assay to Select High-Binding Antibody and Predict Therapy Response for Personalized 64Cu-Intraperitoneal Radioimmunotherapy against Peritoneal Dissemination of Pancreatic Cancer: A Feasibility Study" International Journal of Molecular Sciences 23, no. 10: 5807. https://doi.org/10.3390/ijms23105807

APA Style

Hihara, F., Matsumoto, H., Yoshimoto, M., Masuko, T., Endo, Y., Igarashi, C., Tachibana, T., Shinada, M., Zhang, M.-R., Kurosawa, G., Sugyo, A., Tsuji, A. B., Higashi, T., Kurihara, H., Ueno, M., & Yoshii, Y. (2022). In Vitro Tumor Cell-Binding Assay to Select High-Binding Antibody and Predict Therapy Response for Personalized 64Cu-Intraperitoneal Radioimmunotherapy against Peritoneal Dissemination of Pancreatic Cancer: A Feasibility Study. International Journal of Molecular Sciences, 23(10), 5807. https://doi.org/10.3390/ijms23105807

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