Monoclonal Mouse Antibody Discovery Introduction

Since 1986, when the first mouse-derived monoclonal antibody was created, there have been more than 100 monoclonal antibody drugs on the market. The rapid development of monoclonal antibodies has brought new hope for the conquest of some intractable diseases. From the initial murine monoclonal antibody to the current technology of preparing fully human antibodies based on transgenic mice, murine antibodies have been playing an important role in the field of antibody development and application. Based on rich practical experience and advanced antibody preparation platform, Creative Biolabs provides comprehensive antibody discovery services to support monoclonal mouse antibody production.

Monoclonal Mouse Antibody Discovery

Mice, as one of the most common rodents, is recognized as a mammalian model organism. The results of the full sequencing of the mouse genome show that it has a high degree of homology with human genes. Compared with other common laboratory animals, mice also have significant advantages such as their small size, low feeding cost, easy maintenance and handling, and high reproductive capacity. In addition, genetic studies on mice are relatively mature, with hundreds of established inbred, outbred, and transgenic mouse strains available for different experimental studies. The process of antibody development can also be described as the development of monoclonal mouse antibodies.

The first generation of monoclonal antibodies is the mouse-based hybridoma monoclonal antibody technology. However, first-generation murine antibodies can be recognized by the human immune system, causing human anti-mouse antibody reactions, which weaken the efficacy of monoclonal antibody drugs and cause serious adverse reactions. Therefore, the clinical application of first-generation monoclonal antibody drugs was greatly restricted. Since then, research on the humanization of murine antibodies has begun. With human-mouse chimeric monoclonal antibodies, humanized monoclonal antibodies, and now fully humanized monoclonal antibodies, we have been able to obtain fully humanized monoclonal antibodies in different ways.

Chimeric antibodies are produced by replacing the constant region sequence of the corresponding mouse antibody gene with the constant region sequence of the antibody producing gene of human origin. This method greatly reduces the immunogenic response produced by the mouse-derived antibody, so that 70% of the antibody's components are human components. The vector is then inserted, and the cells are transfected to produce the antibody. Although the antigen-recognizing sequences in the variable region of the antibody make up only a very small fraction of the chimeric monoclonal antibody, the mouse-derived gene is still present.

Humanized antibodies are proteins expressed after genetic recombination of the 6 CDRs in the variable region of a murine monoclonal antibody with the relatively conserved variable region framework region of a human. The degree of humanization can be up to 95%, but most antibodies that have been modified by humanization have reduced affinity and specificity and are highly immunogenic.

Fully human antibodies, that is, the amino acid sequences that make up the antibody, are all derived from humans. There are now four routes that can be used to prepare fully human antibodies. The first is phage display technology, which is also a more mature monoclonal antibody preparation technology. Rapid screening of monoclonal antibodies is possible by performing phage display library construction according to experimental needs, and the limitations of hybridoma technology can be avoided. Meanwhile, the construction of immune antibody libraries based on phage display technology can efficiently screen antibodies with high specificity and affinity against specific immunogens. The second is yeast display technology. It can improve the correctness of antibody folding and the three-dimensional structure of post-expression modification, thus improving the affinity and stability of protein binding on the cell surface. The third is to obtain fully human antibodies by transgenic mice. Simply put, human antibody heavy chain and light chain genes are transferred into mice with defective antibody genes, and the mice are then immunized with the antigen to obtain fully human antibodies. This technique avoids the need for a single humanized modification of each antibody, resulting in reduced antibody preparation costs and shorter development cycles. The fourth is the single B-cell antibody preparation technique. This technology bases on the principle that EBV can infect normal B cells in vitro and turn them into lymphocyte cell lines with unlimited transmissions to prepare hybridoma cells that secrete human single antibodies.

Creative Biolabs has a wealth of knowledge and experience in monoclonal antibody discovery. We would be happy to share with you our knowledge and experience related to monoclonal mouse antibody discovery.

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