Bi-specific T-cell engager

BiTE antibodies (of English. Bi -specific T -cell engagers ) are artificial bispecific monoclonal antibodies. They consist of two scFv fragments, which are joined together through a peptide bridge. One of the two scFv fragments has a selectivity for an antigen on a target cell. The other scFv fragment is capable of specifically binding to the surface proteins of T-cells. In this manner can be specifically a T -cell mediated immune response against specific target cells such as tumor cells is controlled, with the aid of BiTE antibodies. Therefore, BiTE antibodies that were largely developed by the biotechnology company Micromet, researched as a possible new option in cancer therapy.

Structure

BiTE antibodies are composed of two scFv fragments and have a molecular mass of about 55 kDa. Each of the scFv fragments each consisting of a variable domain of the light (VL ) and a variable domain of the heavy chain (VH ) of a conventional monoclonal antibody. These four domains are connected by peptide bonds to a single amino acid chain. For the development and production of this structural feature is an advantage over conventional, consisting of a total of four chains IgG antibodies. BiTE antibodies can be put together with the help of molecular biological methods, encoded by a single gene and recovered by conventional biotechnological methods using eukaryotic cell lines.

Function

The two scFv fragments, from which a BiTE antibody is constructed are able to bind to bispecific two distinct target proteins. An scFv fragment binds more definition to a surface protein of the T cells, usually the CD3 receptor. The second scFv is directed against a surface protein that is expressed as selectively as possible to the target cell. By binding to the corresponding target proteins BiTE antibodies lead to a linking of a target cell with a T cell. The T- cell is activated in this way and begins cytotoxic proteins, such as the pore-forming protein perforin and granzyme that trigger programmed cell death ( apoptosis) to produce and release. As a result, the target cell will be destroyed.

This mechanism is of the natural function of cytotoxic T cells modeled. However, the T-cell -mediated recognition and destruction of a target cell using BiTE antibodies is independent of the involvement of the major histocompatibility complex ( MHC).

Use

BiTE antibodies are particularly discussed as a possible new option in cancer therapy. The BiTE antibody Blinatumomab, which is directed against CD3 and CD19, is currently being tested in clinical trials. Additional BiTE antibodies against CD3 and EpCAM, HER2/neu, EGFR, CD66e, CD33, EphA2 or MCSP are in development.