MUC1-specific targeting immunotherapy with bispecific antibodies: Inhibition of xenografted human bile duct carcinoma growth

Yu Katayose, Toshio Kudo, Masanori Suzuki, Masao Shinoda, Susumu Saijyo, Naoki Sakurai, Hisaaki Saeki, Kenji Fukuhara, Kohzo Imai, Seiki Matsuno

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38 Citations (Scopus)

Abstract

For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we synthesized two bispecific antibodies (BsAbs), MUC1 x CD3 BsAb constructed with MUSE11 (anti-MUC1 tumor antigen) and OKT-3 (anti- CD3), and MUC1 x CD28 BsAb constructed with MUSE11 and 15E8 (anti-CD28) antibodies. These two BsAbs reacted well with both MUC1-positive target tumor cells and effector lymphokineactivated killer (LAK) cells. Investigation of in vitro cytotoxicity [3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide assay] revealed that the MUC1 x CD3 BsAb could antigen-specifically enhance the cytotoxicity of LAK cells. Addition of the two BsAbs (MUC1 x CD3 BsAb plus MUC1 x CD28 BsAb) in vitro resulted in a 60% cytotoxicity, similar to that obtained with BsAb (MUC1 x CD3) alone. Interleukin 12-induced LAK cells demonstrated far greater cytotoxicity (50%) than their interleukin 2- induced counterparts (LAK cells), and this was also enhanced by the BsAbs. When 2 x 107 LAK cells sensitized with both kinds of BsAbs were administered four times i.v. to BDC-grafted severe combined immunodeficient mice (tumor size 5 mm in diameter), inhibition of tumor growth was observed. Thus, BsAb- LAK therapy for control of BDC warrants clinical trials.

Original languageEnglish
Pages (from-to)4205-4212
Number of pages8
JournalCancer Research
Volume56
Issue number18
Publication statusPublished - 1996 Sep 15

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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