Mammalian Cell Display System Overview

About 20 years ago, in vitro display techniques such as phage display, yeast display, bacterial display, and ribosome display began to be used for antibody screening. With the development of technology, these in vitro display techniques have been improved and have been widely used in different biomedical fields. However, these in vitro techniques have some drawbacks. Mammalian cell surface display technology may be able to make up for these drawbacks. Antibodies based on mammalian cell display technology are the closest to natural higher biological protein molecules in terms of molecular structure, physicochemical properties, and biological functions. Based on our rich experience and advanced mammalian cell display platform, Creative Biolabs provides comprehensive mammalian cell display services to support the development and application of antibodies.

Fig 1. Human cells. (Creative Biolabs Authorized)

Mammalian Cell Surface Display

In the application of recombinant antibodies, common display technologies include yeast surface display, phage display, bacterial display, ribosome display technology, etc., most of which are based on prokaryotic expression systems. In addition, in prokaryotic expression systems, the codons selected during protein expression are different from those of eukaryotic cells. Mammalian cell surface display technology can effectively solve the above problems. It can not only display full-length antibodies but also use the eukaryotic expression system to guide the correct folding of proteins and provide a variety of post translational processing functions, such as complex N-glycosylation and accurate O-glycosylation. Therefore, the displayed antibodies are the closest to the natural protein molecules of higher organisms in terms of molecular structure, physicochemical properties, and biological functions. In addition, they are stably expressed and secreted at a high level in mammalian cells. Therefore, mammalian cell display technology has potential advantages that other technologies do not have.

Mammalian cell display technology applies recombinant DNA technology to express the gene sequence to be displayed in fusion with the transmembrane sequence of the mammalian cell receptor, and then displays the overexpressed recombinant exogenous proteins on the surface of mammalian cells by utilizing the membrane localization of the transmembrane region of the receptor. Taking the mammalian cell antibody display technology as an example, the technology mainly utilizes cell surface expression of antibodies to screen and obtain recombinant therapeutic monoclonal antibodies. The steps include vector construction, cell transfection, expression of antigenic epitopes, and antigen recognition. The first two steps can be collectively referred to as building a mammalian cell surface display antibody library. The last step is also known as the enrichment and screening of antibodies that bind specifically to the target.

There are two of the most widely used mammalian cell expression systems in mammalian cell display technology. They are Chinese hamster ovary cells and human embryonic kidney 293 cells. The vectors screened for these expression systems include pcDNA series vectors, pDGB vectors, and some viral vectors.

Although mammalian cell display technology has many advantages and development potential, there are still a number of problems to be solved. The library diversity of most mammalian cell display antibody libraries is only 10⁶–10⁸, which is much lower than that of phage display antibody libraries, which can reach 10¹⁰–10¹¹. In addition, it is more difficult to operate, the cycle time is longer, and the cost is relatively high. During plasmid transfection or virus infection, it is also more difficult for the operator to ensure that only one exogenous DNA enters a single cell, which may cause some interference in the later antibody screening.

Creative Biolabs has a wealth of knowledge and experience in surface display technology. We would be happy to share with you our knowledge and experience related to mammalian cell display systems.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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