Papers

Peer-reviewed International journal
Mar, 2017

Uptake of 111In-labeled fully human monoclonal antibody TSP-A18 reflects transferrin receptor expression in normal organs and tissues of mice.

Oncology reports
  • Aya Sugyo
  • ,
  • Atsushi B Tsuji
  • ,
  • Hitomi Sudo
  • ,
  • Fumiko Nomura
  • ,
  • Hirokazu Satoh
  • ,
  • Mitsuru Koizumi
  • ,
  • Gene Kurosawa
  • ,
  • Yoshikazu Kurosawa
  • ,
  • Tsuneo Saga

Volume
37
Number
3
First page
1529
Last page
1536
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.3892/or.2017.5412
Publisher
SPANDIDOS PUBL LTD

Transferrin receptor (TfR) is an attractive molecule for targeted therapy of cancer. Various TfR-targeted therapeutic agents such as anti-TfR antibodies conjugated with anticancer agents have been developed. An antibody that recognizes both human and murine TfR is needed to predict the toxicity of antibody-based agents before clinical trials, there is no such antibody to date. In this study, a new fully human monoclonal antibody TSP-A18 that recognizes both human and murine TfR was developed and the correlation analysis of the radiolabeled antibody uptake and TfR expression in two murine strains was conducted. TSP-A18 was selected using extracellular portions of human and murine TfR from a human antibody library. The cross-reactivity of TSP-A18 with human and murine cells was confirmed by flow cytometry. Cell binding and competitive inhibition assays with [111In]TSP-A18 showed that TSP-A18 bound highly to TfR-expressing MIAPaCa-2 cells with high affinity. Biodistribution studies of [111In]TSP-A18 and [67Ga]citrate (a transferrin-mediated imaging probe) were conducted in C57BL/6J and BALB/c-nu/nu mice. [111In]TSP-A18 was accumulated highly in the spleen and bone containing marrow component of both strains, whereas high [67Ga]citrate uptake was only observed in bone containing marrow component and not in the spleen. Western blotting indicated the spleen showed the strongest TfR expression compared with other organs in both strains. There was significant correlation between [111In]TSP-A18 uptake and TfR protein expression in both strains, whereas there was significant correlation of [67Ga]citrate uptake with TfR expression only in C57BL/6J. These findings suggest that the difference in TfR expression between murine strains should be carefully considered when testing for the toxicity of anti-TfR antibody in mice and the uptake of anti-TfR antibody could reflect tissue TfR expression more accurately compared with that of transferrin-mediated imaging probe such as [67Ga]citrate.

Link information
DOI
https://doi.org/10.3892/or.2017.5412
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28184946
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000396186600027&DestApp=WOS_CPL
ID information
  • DOI : 10.3892/or.2017.5412
  • ISSN : 1021-335X
  • eISSN : 1791-2431
  • Pubmed ID : 28184946
  • Web of Science ID : WOS:000396186600027

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