CD3× anti-nitrophenyl bispecific diabodies: Universal immunotherapeutic tools for retargeting T cells to tumors

✍ Scribed by Oliver Manzke; Kevin J. Fitzgerald; Philipp Holliger; Jochen Klock; Mary Span; Bernd Fleischmann; Juergen Hescheler; Liu Qinghua; Kevin S. Johnson; Volker Diehl; Hennie R. Hoogenboom; Heribert Bohlen

• Book ID: 101235268
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 184 KB
• Volume: 82
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990827)82:5<700::aid-ijc13>3.0.co;2-2

✦ Synopsis

We developed a universal recombinant bispecific molecule (BiMol) that is capable of redirecting cytotoxic T cells to tumor cells via tagged anti-tumor ligands such as antibody fragments or cytokines. A recombinant bispecific diabody with binding specificities for the CD3 molecule on T cells as well as for the hapten nitrophenyl (NIP) was produced. This bispecific molecule is capable of redirecting cytotoxic T cells to kill a series of malignant cells, including B cell lymphoma,

Hodgkin's lymphoma, and colon carcinoma via NIP-conjugated ligands to tumor-associated antigens. Cytotoxic activity of the diabody was found to be comparable to tetradomaderived bispecific antibodies with similar specificities. Our findings demonstrate that universal CD3؋anti-NIP diabodies could be used for T cell based cellular immunotherapy in a variety of human malignancies. Additionally, these bispecific molecules allow fast and economic testing of tumor-associated antigens on malignant cells for their potential use as immunotherapeutic target structures if corresponding hapten-conjugated antibodies or ligands are available.