With many years of experience in bispecific antibodies (BsAbs) development, Creative Biolabs provides a novel LUZ-Y BsAb generation platform. Our experts are proud to offer a wide range of BsAbs with this novel technique to accelerate your research process from lab to clinical stage.
The capacity of BsAbs to simultaneously bind two unique antigens has tremendous clinical potential. Various formats have been developed for generating BsAbs from either bacterial or mammalian cells. Nevertheless, a majority of methods used to produce BsAbs form antibody-like structures that diverge significantly from the structure of archetype human IgG, and those that do method structural similarity to native antibodies are usual challenging to engineer and manufacture. Although the two-in-one Ab is structurally similar to the native IgG, production of this type of BsAbs remains a challenge.
Creative Biolabs has developed a unique platform for the mammalian cell production of BsAbs that differ from their parental mAbs with just a single point mutation per heavy chain. The key point of this platform is the accretion of a leucine zipper to the C terminus of the CH3 domain of the antibody which is adequate to drive the heterodimeric assembly of antibody heavy chains and enables to be readily removed post-purification. After purification and proteolytic processing, LUZ-Ys (refers to antibodies with a leucine zipper to induce heterodimerization of two different HCs) differ from their parental mAbs with a single Lys to Ala mutation at residue 222 in the hinge region of the HC. It has proved that these antibodies enable to specifically bind their antigens with high affinity, besides, in the case of the bispecific formats, discriminately and non-competitively. Based on this well established platform, we developed a full range of antibody constructs, such as BsAbs that utilize a general light chain, one-armed Abs, and BsAbs that pair light chains to their cognate heavy chains by peptide tethers.
Figure 1. This figure shows the four LUZ-Y formats. a, the one-armed LUZ-Y; b, the common LC LUZ-Y; c, the tethered LUZ-Y; d, the tethered LUZ-Y with Furin cleavable tethers. (Wranik, B. J., 2012)
The major advantage of LUZ-Y BsAb is that it can greatly avoid cognate light chains and heavy chains mispairing, and make the products display more similar features to native IgGs compared with other techniques, such as knobs-into-holes, strand-exchange engineered domain (SEED), and electrostatic steering.
Utilizing this technique, we offer customers the following antibody constructs:
With the well-established LUZ-Y BsAb generation platform, the experienced scientists here at Creative Biolabs are dedicated to helping you develop therapeutic BsAbs. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.
1. Wranik, B. J.; et al. LUZ-Y, a novel platform for the mammalian cell production of full-length IgG-bispecific antibodies. Journal of Biological Chemistry. 2012, 287(52): 43331-43339.
2. Spiess, C.; et al. Alternative molecular formats and therapeutic applications for bispecific antibodies. Molecular immunology. 2015, 67(2): 95-106.