Humanization, a Milestone in Antibody Drug Development Strategy

2024-04-18 12:29:35 Health and Fitness

684

Antibody drug is the main force of modern biotechnology industry, accounting for more than 50% of the global biological products market, and is one of the fastest growing subdivision fields.

Since the first monoclonal antibody drug was approved by FDA in 1986, over 50 antibody drugs have been authorized by now around the world, whose global sales increased from 370 million US dollars in 1997 to more than 70 billion US dollars in 2015, Presently, mAb drugs occupy 6 seats among the top 10 drugs sold in the world.

Monoclonal antibody (mAb) is the most outstanding and mature technology in the field of antibody drug, supporting the tumor targeting drug, immuno checkpoint blocking drug, or the popular CAR-T technology that all share huge investment market. Conventionally speaking, the typical mouse monoclonal antibody needs to undergo a series of engineering modifications to improve its pharmacokinetics in vivo.

Common strategies for antibody engineering include antibody humanization, antibody affinity maturation, antibody stability improvement, chimeric antigen receptor (CAR) construction, scFv/Fab construction, FC modification, or antibody aggregation reduction.

Antibody Humanization
Mouse mAb?the initial monoclonal antibody to enter the clinic tests can induce human anti-mouse antibody (HAMA) reaction, which might result in efficacy neutralization, allergic reaction, and other immunologic manifestations. To solve these problems, many researchers tried to make transition of mouse antibodies to human antibodies, but they are sometimes restricted by lab & equipment shortage. Different companies have similar technology paths in the field of antibody humanization, but how to obtain the most humanized monoclonal antibody while maintaining its high affinity for the target protein is a touchstone. Creative Biolabs, a conscientious CRO with over 10 years of history, is providing one-stop solutions to help.

Associated approaches:
CDR Grafting & SDR Grafting are based upon the complementarity determining region grafting platform characterized by randomly distributed framework residues, which is embedded with 6 CDR loops comprising the antigen-binding site.

Chain shuffling composes another crucial approach that has been optimized with the construction and screening of 2 chimeric phage display libraries.

The humanized IgG library screening allows selection of full-size IgG humanized antibodies that keep the original affinity of mouse antibody, which can apply to the downstream operations so as to avoid time waste on converting scFv to IgG

Stricter requirements can find solutions, like obtaining a higher standard humanized antibody for tests on drugs, with the help of Creative Biolabs?s non-human primates? antibody humanization operation. As is known that the drugs developed from mouse antibody, if entered the clinical stages, had better get tested on monkeys that share similar genetic characteristics with humans. The featured solution can deal with the problem at the source.

The procedure does not terminate after humanization in that the affinity of antibody obtained by humanization or phage display library technology to target antigen will not be satisfactory, which is not conducive to reducing the clinical use of therapeutic antibody and side effects. Therefore, affinity maturation will take over the ?semi-manufactures? for optimization to better fit in with future clinical usage.

Due to the development of humanized mAb, phage display technology, transgenic mice and other related technologies, a large number of patented antibodies gradually entered the clinical application stage, which was quickly accepted by the market. Many enterprises spent millions, setting off another upsurge of antibody drug R&D around 2010. Based on the current trend, it is predictable that the patent related to antibody drugs will maintain a stable growth period, followed by more antibody drugs entering the market.