For decades, traditional polyclonal and monoclonal antibodies (mAbs) have driven progress in many different fields of research. More recently, they have been complemented by recombinant antibodies that offer opportunities for modification and engineering. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in the patient treatment. Moreover, antibody engineering technologies were developed and explored to obtain chosen characteristics of selected leading candidates such as high affinity, low immunogenicity, improved functionality, improved protein production, improved stability, and others.
Fig.1 Therapeutic antibody engineering. (Ministro, 2019)
Antibody engineering was rooted in hybridoma technology. In 1975, Köhler and Milstein developed and described a revolutionary technique for the generation of mAbs, based on the immortalization of mouse B cells through fusion with myeloma tumor cells, subsequently licensed in 1986. This murine mAb was unsatisfactory due to their very short half-life in serum, poor or absent activation of human effector functions, and undesirable stimulation of human anti-mouse antibody responses in patients. The breakthrough technology of antibody gene cloning and expression in 1989 revolutionized the antibody engineering technologies. The ability to manipulate and recombine genes ushered in a second generation of therapeutic mAbs known as chimeras. Humanized mAbs are an extension of the chimera strategy. Both of them generate anti-drug antibodies or decrease the ability of the antibody to interact with its antigen. The newest generation of therapeutic antibodies includes what are referred to as fully human mAbs which carry a lower risk for inducing immune responses in humans than mouse or chimeric antibodies.
Fig.2 From murine to humanized antibodies. (Kandari, 2021)
The scope of antibody-based biologics is vast, and it is likely to solve many unmet clinical needs in future. The majority of attention is now devoted to developing innovative technologies for manufacturing and engineering antibodies, better suited to satisfy human needs. Antibody engineering consists of modifying mAbs sequences and/or structures to either enhance or dampen their functions. Antibody engineering techniques is used to construct complete antibodies (Fc engineering, antibody drug conjugates or other modification) and various types of antibody fragments (fv, vHH, fab, scfv, bispecific format, etc.) to enhance therapeutic applications. The expansion of strategies is related to discovery technologies of mAbs (phage display, yeast display, ribosome display, bacterial display, mammalian cell surface display, mRNA display, DNA display, transgenic animal, and human B-cell derived).
Fig.3 Antibody engineering and its therapeutic applications. (Kandari, 2021)
Creative Biolabs offers a wide range of antibody engineering services that complement your research and accelerate the process from development to clinical use. In addition, we aslo provide ViroAntibody discovery and customized services. Please feel free to contact us for further discussion.