CD3x anti-nitrophenyl bispecific diabodies: Universal immunotherapeutic tools for retargeting T cells to tumors

We developed a universal recombinant bispecific molecule (BiMol) that is ca pable 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 c ells, including B cell lymphoma, Hodgkin's lymphoma, and colon carcinoma vi a NIP-conjugated ligands to tumor-associated antigens, Cytotoxic activity o f the diabody was found to be comparable to tetradoma- derived bispecific a ntibodies with similar specificities. Our findings demonstrate that univers al CD3xanti-NIP diabodies could be used for T cell based cellular immunothe rapy in a variety of human malignancies. Additionally, these bispecific mol ecules allow fast and economic testing of tumor-associated antigens on mali gnant cells for their potential use as immunotherapeutic target structures if corresponding hapten-conjugated antibodies or ligands are available. Int . J, Cancer 82:700-708, 1999. (C) 1999 Wiley-Liss, Inc.