Why Does Antibody Humanization Still Matter?

Posted by Jerry Carter on May 2nd, 2019

Therapeutic antibodies play a crucial part in protecting human health. To date, they have been widely used for the prophylaxis, diagnosis and treatment of a host of diseases. Since the exogenous antibodies probably give rise to immune response in host human bodies, the humanization of antibodies has been of apparent importance. The purpose of humanization is exactly for reducing the immunogenecity. That’s why humanization technology has elicited considerable attention from the academia and industry.

Thus far, through over twenty years of development, the humanization technology has improved significantly. And it’s being widely used in almost every antibody-based research. Besides, the related technology has been developing in a quite fast manner. Nowadays, we go so far as to be able to acquire full human antibodies which exhibit little immunogenecity in human bodies and thus exclude the need for the tedious and laborious humanization process. Then, why do we still need antibody humanization?

First, the number of platforms generating full human antibodies is few, far less than meeting the colossal market demands. In the past years, the human antibodies from transgenic mice have increased rapidly, the humanization platforms appear relatively limited and exclusive. Related reports show that all of the eight approved human antibodies derive from only three platforms. Therefore, the current antibody humanization platforms cannot occupy the majority of market shares, at least within the next coming years.

Second, there exists disagreement about the human antibody manufacturing. Currently, full human antibodies are generated mainly by use of mice. Some people debate over the germline repertoire engineered into the mouse immune system. They question the engineered system’s capacity of producing a broad enough range of human antibodies with the limited repertoire. Importantly, since human antibodies from transgenic mice are essentially hybrids of mouse and human components (for example, human immunoglobulin sequences and mouse signalling molecules), some academics expressed concern about the resulting human antibodies, which may cause some unknown dangers.

Third, the current humanization technology is sufficiently mature to lower the immunogenicity of xenogeneic antibodies to an appropriate level. At present, the three common methods for reducing the immunogenicity are CDR Grafting, human framework, and phage display technologies. Of the three methods, the CDR Grafting is the most popular one. This method was originally developed by Greg Winter in 1986, and still remains one of the most popular techniques for the production of therapeutic antibodies. The modern version of this method substantially reduces the potential immunogenicity of exogenous antibodies, so that it can act as an alternative of the full human antibodies. Moreover, there’s a notable growth in associated platforms.

Given the three reasons above, we can safely conclude that antibody humanization still matters, despite the emergence of full human antibodies. According to concerned data, an increasing number of companies are devoting themselves to screening the full B cell repertoire of various host species, such as rabbits, avian and llamas, so as to select the optimum monoclonal antibodies with the correct characteristics. Besides, the transgenic animals will continue to play important roles as vehicles in antibody humanization.

Like it? Share it!


Jerry Carter

About the Author

Jerry Carter
Joined: January 2nd, 2019
Articles Posted: 13

More by this author