This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Katayose, Y. Articles by Matsuno, S. Search for Related Content PubMed PubMed Citation Articles by Katayose, Y. Articles by Matsuno, S.

MUC1-specific Targeting Immunotherapy with Bispecific Antibodies: Inhibition of Xenografted Human Bile Duct Carcinoma Growth¹

First Department of Surgery, Tohoku University School of Medicine, 1-1 Seiryomachi [Y. K., M. Su., M. Sh., S. S., N. S., K. F., S. M.] and Cancer Cell Repository, Institute of Development, Aging and Cancer, Tohoku University, 4-I Seiryomachi [T. K., H. S.], Aoba-ku, Sendai 980-77, and Department of Internal Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060, [K. I.], Japan

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 lymphokine-activated 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.

¹ This work was supported in part by Grant-in-Aid for Cancer Research 06279101 from the Ministry of Education, Science, Sports and Culture of Japan.

² To whom requests for reprints should be addressed. Phone/Fax: (81) 22-717-8573.

Received 5/ 3/96. Accepted 7/16/96.

This article has been cited by other articles:

				K. Makabe, T. Nakanishi, K. Tsumoto, Y. Tanaka, H. Kondo, M. Umetsu, Y. Sone, R. Asano, and I. Kumagai Thermodynamic Consequences of Mutations in Vernier Zone Residues of a Humanized Anti-human Epidermal Growth Factor Receptor Murine Antibody, 528 J. Biol. Chem., January 11, 2008; 283(2): 1156 - 1166. [Abstract] [Full Text] [PDF]

				U. Reusch, M. Sundaram, P. A. Davol, S. D. Olson, J. B. Davis, K. Demel, J. Nissim, R. Rathore, P. Y. Liu, and L. G. Lum Anti-CD3 x Anti-Epidermal Growth Factor Receptor (EGFR) Bispecific Antibody Redirects T-Cell Cytolytic Activity to EGFR-Positive Cancers In vitro and in an Animal Model Clin. Cancer Res., January 1, 2006; 12(1): 183 - 190. [Abstract] [Full Text] [PDF]

				A. M. McCall, L. Shahied, A. R. Amoroso, E. M. Horak, H. H. Simmons, U. Nielson, G. P. Adams, R. Schier, J. D. Marks, and L. M. Weiner Increasing the Affinity for Tumor Antigen Enhances Bispecific Antibody Cytotoxicity J. Immunol., May 15, 2001; 166(10): 6112 - 6117. [Abstract] [Full Text] [PDF]

				S.-i. Takemura, R. Asano, K. Tsumoto, S. Ebara, N. Sakurai, Y. Katayose, H. Kodama, H. Yoshida, M. Suzuki, K. Imai, et al. Construction of a diabody (small recombinant bispecific antibody) using a refolding system Protein Eng. Des. Sel., August 1, 2000; 13(8): 583 - 588. [Abstract] [Full Text] [PDF]

				A. Baruch, M.-l. Hartmann, M. Yoeli, Y. Adereth, S. Greenstein, Y. Stadler, Y. Skornik, J. Zaretsky, N. I. Smorodinsky, I. Keydar, et al. The Breast Cancer-associated MUC1 Gene Generates Both a Receptor and Its Cognate Binding Protein Cancer Res., April 1, 1999; 59(7): 1552 - 1561. [Abstract] [Full Text] [PDF]