T-Cell Engagement

Antibodies with a dual specificity in their binding arms usually do not occur in nature and, therefore, had to be developed using recombinant DNA or cell fusion technology. Amongst the first bispecific antibodies, were constructs designed to redirect T cells against cancer target cells.

Cancer target cells are killed when cytotoxic T-lymphocytes are directed to tumour cells and simultaneously triggered by one arm of the bispecific antibody that interacted with the T-cell receptor (TCR)–CD3 complex. The use of the monomorphic CD3 complex for triggering T cells circumvents the restrictions of clonotypic T-cell specificity and enables a polyclonal cytotoxic T-cell response against tumour cells expressing the target antigen, which is recognized by the second arm of the bispecific antibody. As a result the induced T-cell cytotoxicity, lysis the tumour cells and the tumour is killed.

It is important to note that cytotoxic T lymphocytes (CTL), which are considered to be the most potent killer cells of the immune system, cannot be engaged by conventional monoclonal antibodies because they lack Fcγ receptors. Therefore bi-(or tri-) specific recombinant antibodies which recruit CTLs have the potential to be much more effective than conventional monoclonal antibody therapies.

Cancer target cells are killed when cytotoxic T-lymphocytes are directed to tumour cells. Clicking this link you can see the efficacy of a Tribody

 targeting a Triple Negative Breast Cancer tumour cell line and destroying it via induced T-cell cytotoxicity,