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

LK Gilliland, MR Clark… - Proceedings of the …, 1988 - National Acad Sciences
LK Gilliland, MR Clark, H Waldmann
Proceedings of the National Academy of Sciences, 1988National Acad Sciences
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 …
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.
National Acad Sciences
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