International Journal of Molecular Sciences (May 2022)

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

  • Fukiko Hihara,
  • Hiroki Matsumoto,
  • Mitsuyoshi Yoshimoto,
  • Takashi Masuko,
  • Yuichi Endo,
  • Chika Igarashi,
  • Tomoko Tachibana,
  • Mitsuhiro Shinada,
  • Ming-Rong Zhang,
  • Gene Kurosawa,
  • Aya Sugyo,
  • Atsushi B. Tsuji,
  • Tatsuya Higashi,
  • Hiroaki Kurihara,
  • Makoto Ueno,
  • Yukie Yoshii

DOI
https://doi.org/10.3390/ijms23105807
Journal volume & issue
Vol. 23, no. 10
p. 5807

Abstract

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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.

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