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The most promising strategy in cancer treatment is to direct cytotoxic T cells to kill tumor cells. The clinical success of CAR-T therapy also highlights the value of using cytotoxic T cells (CTL) to treat cancer. This can be achieved using dual targeting antibodies that simultaneously bind to tumor-specific antigens on tumor cells and CD3 on T cells, bringing these cells in close proximity and causing the T cells to kill tumor cells. Most bispecific antibodies are constructed as heterodimers, which have monovalent binding to antigens highly expressed on tumor cells and CD3 on T cells.
At Creative Biolabs, we have developed a novel tetravalent bispecific (TetraBi) platform: a tumor-associated antigen specific, T-cell engaging antibody that provides significant advantages over traditional BiTEs. Compared with the traditional bispecific antibody, the TetraBi format offers several significant advantages over other bispecific antibody formats and other approaches to T cell-based therapy.
We provide the generation and characterization services of tetravalent, bispecific antibody derivatives to enhance the anti-tumor activity mediated by T cell engager. Their bispecific molecules are composed of an IgG antibody, designated the master or parent module, with scFvs of different specificities coupled to the C terminus of the heavy chain. The bispecific molecule contains flexible peptide sequences between the VH and VL domains and between the parent IgG and other scFv moieties to form scFv. We chose to apply the well-known sequence motif (G4S) to these two connections. In contrast to monospecific antibodies, this novel form of TetraBi antibody can simultaneously involve different target antigens in a bivalent and monovalent manner in the tumor microenvironment and has potential therapeutic significance. In addition, it provides a greater therapeutic index compared to the more traditional bispecific form characterized by monovalent recognition of tumor antigens.
Fig.1 Schematic diagram of tetravalent bispecific antibody.
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