With state-of-the art facilities, experienced scientists in antibody engineering field, Creative Biolabs provides various recombinant antibodies by fusing bispecific antibody (BsAb) with human serum albumin (HSA).
In the past years, a variety of small recombinant BsAb formats are comprised of only the variable regions, which decide the binding unit of an antibody, have been designed. These formats such as single chain diabodies (scDb), bispecific diabodies (Db), and tandem scFv (taFv), have been used successfully in vitro and in vivo for the retargeting of cytotoxic T lymphocytes to tumor cells. Nevertheless, these small BsAb molecules with molecular masses between 50 and 60 kDa are quickly cleared from circulation with an incipient half-life of less than 30 min. This displayed some problems on therapeutic applications, for example, demand of high doses and repeated injections or infusions. Therefore, therapeutic applications should benefit from an enhancement of serum half-life. In order to promote pharmacokinetic properties of small molecules, the majority of attempts have been directed so far to improve the apparent molecular size of the recombinant protein.
Novel methods to increase pharmacokinetics of small proteins are relied on binding to or fusion with long-circulating serum proteins, including albumin. Albumin, a monomeric protein of 67 kDa generated in the liver, is the most abundant protein in the blood plasma. Albumin is able to regulate the osmotic pressure of plasma, it also has several physiologic functions, such as the transport of metabolites like long chain fatty acids, steroid hormones, bilirubin. Importantly, albumin binds with high affinity to a great number of drugs affecting their pharmacokinetic properties. According to these properties, HAS has been applied as macromolecular carrier for drug delivery or diagnostic purpose.
Figure 1. Schematic presentation of bispecific antibody-HSA fusion proteins.
To solve the problem mentioned above, scientists from Creative Biolabs fuse BsAbs with long-circulating serum protein: human serum albumin (HSA), which has a high affinity and a strong stability. This protein has been widely used in therapy and diagnostic researches. With the mammalian expression system, we have produced three forms of recombinant BsAb HSA fusion proteins, which are based on tandem scFv, single chain diabody, and two different single chain Fv fragments, respectively. These novel BsAb molecules displayed specific binding to both antigens and enable to retarget and activate effector cells in vitro to various extents. Contrasted with the parental antibodies, all bispecific albumin fusion proteins exhibited strong improvement of the serum half-life in mice.
By leveraging advanced antibody engineering platforms, Creative Biolabs offers bispecific antibody-HSA fusion proteins with the highest standard for quality. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.
1. Müller, D.; et al. Improved pharmacokinetics of recombinant bispecific antibody molecules by fusion to human serum albumin. Journal of Biological Chemistry. 2007, 282(17): 12650-12660.
2. Kenanova, V. E.; et al. Tuning the serum persistence of human serum albumin domain III: diabody fusion proteins. Protein Engineering, Design & Selection. 2010, 23(10): 789-798.