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 Hsieh-Ma, S. T. Articles by Ring, D. B. Search for Related Content PubMed PubMed Citation Articles by Hsieh-Ma, S. T. Articles by Ring, D. B.

In Vitro Cytotoxic Targeting by Human Mononuclear Cells and Bispecific Antibody 2B1, Recognizing c-erbB-2 Protooncogene Product and Fc Receptor III

Chiron Corporation, Emeryville, California 94608

² To whom requests for reprints should be addressed, at Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608.

Bispecific murine monoclonal antibody 2B1, possessing dual specificity for the human c-erbB-2 protooncogene product and human Fc receptor III (CD16) was evaluated for the ability to promote specific lysis of c-erbB-2-positive tumor cells in vitro. In short-term ⁵¹Cr release assays with human mononuclear cells as effectors and SK-Br-3 human breast cancer cells as targets, neither parental antibody of 2B1 mediated significant specific lysis, but bispecific antibody was as active as a chemical heteroconjugate, with 5 ng/ml of 2B1 causing half-maximal lysis at an effector/target ratio of 20:1 and 2 ng/ml 2B1 causing half-maximal lysis at an E/T ratio of 40:1. The cytotoxic targeting activity of 2B1 F(ab')₂ fragment was the same as that of whole bispecific antibody, and the activity of whole 2B1 was not reduced when assays were performed in 100% autologous human serum, indicating that 2B1 binds effector cells through the CD16-binding site derived from parental antibody 3G8 rather than through its Fc portion. Variable inhibition of 2B1-mediated lysis was observed when autologous polymorphonuclear leukocytes from different donors were added to mononuclear effector cells at a 2:1 ratio; this inhibition was overcome at higher antibody concentration. 2B1 bispecific monoclonal antibody was also able to mediate targeted cytolysis using whole human blood as a source of effector cells or using effector or target cells derived from ovarian cancer patients.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/10/92. Accepted 10/ 6/92.

This article has been cited by other articles:

				L. S. Shahied, Y. Tang, R. K. Alpaugh, R. Somer, D. Greenspon, and L. M. Weiner Bispecific Minibodies Targeting HER2/neu and CD16 Exhibit Improved Tumor Lysis When Placed in a Divalent Tumor Antigen Binding Format J. Biol. Chem., December 24, 2004; 279(52): 53907 - 53914. [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]

				R. Zhang and L. J. DeGroot A Monoclonal Antibody against Rat Calcitonin Inhibits the Growth of a Rat Medullary Thyroid Carcinoma Cell Line in Vitro Endocrinology, April 1, 1997; 138(4): 1697 - 1703. [Abstract] [Full Text] [PDF]

				P. F. Bongiorno, R. I. Whyte, E. J. Lesser, J. H. Moore, M. B. Orringer, and D. G. Beer Alterations of K-ras, p53, and erbB-2/neu in human lung adenocarcinomas J. Thorac. Cardiovasc. Surg., February 1, 1994; 107(2): 590 - 595. [Abstract] [Full Text]