Katsuyuki Mitomo

Abstract 4323: Antibodies against TfR inhibit growth of tumor cells both in vitro and in vivo.

Transferrin receptor (TfR) is a type II transmembrane glycoprotein regulating intracellular uptake of iron, and is therefore involved in cell survival and proliferation. TfR has been reported to be more abundantly expressed in dividing cells, e.g. malignant cells, than in quiescent cells, as in most normal cells. Therefore, it is regarded as a potential target for usage in cancer therapy. In the present study, we generated a panel of human anti-TfR antibodies and evaluated its anti-tumor effect both in vitro and in vivo. We found that several antibodies inhibited cell proliferation in various tumor cells, and elicited antibody dependent cellular cytotoxicity (ADCC) activity. Among these antibodies, PPMXT001 and PPMXT002 exerted a significant anti-tumor activity in several xenograft models. PPMXT001 completely suppressed tumor growth in a pancreatic cancer model (MIAPaCa2). PPMXT002 also inhibited tumor growth by 60∼80% in several solid cancer xenograft models including bladder cancer, colon cancer, prostate cancer, and pancreatic cancer. These findings showed that PPMXT001 and PPMXT002 could be potent candidates for developing antibody therapeutics to treat cancer. Citation Format: Lilin Zhang, Yoshinori Ukai, Fumiko Nomura, Youichi Aikawa, Yoko Kayukawa, Katsuyuki Mitomo, Katsushi Kouda, Romi Kodaka, Gene Kurosawa, Yoshikazu Kurosawa, Kazuhiro Morishita, Yukio Sudo. Antibodies against TfR inhibit growth of tumor cells both in vitro and in vivo . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4323. doi:10.1158/1538-7445.AM2013-4323