Universal bispecific antibody for targeting tumor cells for destruction by cytotoxic T cells.

Journal article

Previous studies have demonstrated that bispecific hybrid antibodies produced by cell-cell fusion or chemically conjugated heteroaggregates can direct cytotoxic T lymphocytes to kill target cells for which they have no intrinsic specificity, a phenomenon we call effector cell retargeting (ECR). These studies used bispecific reagents with one specificity directed to CD3 or Ti on the effector cell and the other directed to a target cell antigen. To avoid the need to create different hybrid hybridomas for each target antigen we have developed a universal means to elicit ECR through the use of an antiglobulin step. We have constructed a bispecific hybrid antibody with dual specificity for CD3 and a rat immunoglobulin light chain allotype. This bispecific antibody could mediate ECR to a range of target cells, each coated with distinct surface-binding rat monoclonal antibodies. A particular advantage of targeting to surface-bound monoclonal antibodies is that all other available effector systems may also attack the same antibody-coated target cell.

Authors: Gilliland, L; Clark, MR; Waldmann, H

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 85
• Issue: 20
• Pages: 7719-7723
• Publication date: 1988-10-01
• DOI: 10.1073/pnas.85.20.7719
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Humans; Antibody-Dependent Cell Cytotoxicity; Antibodies, Monoclonal; Thymoma; Hybridomas; Antibody Specificity; Immunoglobulin Light Chains; Mice; Animals; Binding, Competitive; Antigens, Differentiation, T-Lymphocyte; Tumor Cells, Cultured; T-Lymphocytes, Cytotoxic