Based on years of experience in antibody discovery and production, Creative Biolabs has developed second to none bispecific antibody (BsAbs) generation services. With our comprehensive platform, we are proud to offer expected tandem scFv with high affinity and low immunogenicity for both academic and clinical purposes.
Just as its name implies, two moieties of scFv string together to form tandem scFv, which has 1+1 antigen-binding. Tandem scFv can be expressed by transfected mammalian cells with four tandem variable regions connected by flexible peptides. Without Fc region, its smaller size (~55 kDa) gives it a short serum half-life, meanwhile, it also ensures a closer proximity to the two targets or the surface of two target cells. Based on tandem scFv, more than moieties of scFv can be stringed to form multi-specific or bispecific, multivalent BsAbs. And CH3 of Fc regions are also engineered into tandem scFv to expand its half life of Fc effector functions, resulting in tandem scFv-CH3 or tandem scFv-Fc.
Figure 1. The constructs of Tandem scFv, Tandem scFv-CH3, Tandem scFv-Fc
Among this class of BsAbs, bispecific T-cell Engagers, known as BiTE, a concept owned by Micromet AG, are most famous. For Bispecific T-cell Engagers, one of its paratopes targets certain tumor-associated cell surface antigen, while the other binds CD3 so as to recruit T cells. Bispecific T-cell engagers ensure a closer proximity to the surface of both T cell and target cell. Once bound to the target antigen expressed on the surface of the respective target cells, binding of CD3 results in activation and polyclonal expansion of cytotoxic T cells. Linking T-cells and target cells result in the generation of an immunological synapse. Following synapse formation, T-cells release perforins and granzymes, and then activate target cell caspases and apoptosis. Video microscopy tests have proven that BiTE antibody constructs are able to serial lysis of tumor cells by engaged T-cells.
Due to cancer cells subverting mechanisms of T-cell control under selective pressure, the antitumor response of T-cells is usually insufficient in part. Improved understanding of the mechanisms of evasion of immune surveillance has result in a number of novel methods of T-cell based immunotherapy. Among of which, BsAbs are a potential strategy. Tandem scFv has more than thousands of times of efficiency in lysing tumor cell compared with other CD3-bispecific or IgG antibodies. Even with a concentration as low as 10 pg/ml in cell culture, BiTEs are still able to direct multiple rounds of target cell lysis by T cells with a low effector cell : target cell ratio. All of these properties have made it one of the most important T cell recruiters for cancer treatment and immune regulation.
Figure 2. Schematic diagram of the mechanism of action for blinatumomab as the BiTE. One arm of blinatumomab binds to CD3, the other binds to CD19. (Wu, J., 2015)
With the well-established antibody generation platforms, the experienced scientists here at Creative Biolabs are dedicated to helping you develop unique tandem scFv and also providing custom Tandem scFv products linking two or more scFvs against hot targets. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.
1. Stieglmaier, J.; et al. Utilizing the BiTE (bispecific T-cell engager) platform for immunotherapy of cancer. Expert Opin Biol Ther. 2015, 15(8):1093-9.
2. Wu, J.; et al. Blinatumomab: a bispecific T cell engager (BiTE) antibody against CD19/CD3 for refractory acute lymphoid leukemia. Journal of hematology & oncology. 2015, 8(1): 104.