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New Generation of Designer Antibody Therapeutics From B Cells

Mar 31, 2014 6:00:43 AM / by Daisy

Scientists use PBMCs from HemaCare to design experiments to improve the clinical response of antibody therapies for cancer and autoimmune diseases

Our bodies are armed with a defense system, ready for action at first sign of disease causing invaders. As part of this defense, an antibody response is mounted in about 5-7 days after first exposure to the invaders. Antibodies are proteins made by B cells and released into blood and tissue fluids. They lock onto bacteria and viruses leading to their eventual demise.

The intriguing fact about antibodies is that they are highly specific. Antibodies interact with only one target site, called the antigen. An antibody-antigen pair can therefore be compared to a lock and key set. Just like there is one key that will click with a lock, so there is one antigen that will click with an antibody.

Scientists fuse B cells with immortal cells to generate antibody-producing factories outside the body in order to generate therapeutic antibodies. Image credits: Wiki Commons Image.

Scientists today have the technology to mass produce antibodies outside the human body. This is done by exposing humans or mice to a specific antigen and then isolating B cells that produce the antibody of interest. These B cells, however, have a short lifespan. So to make these B cells immortal, they are fused with another cell type. As an analogy, this would be comparable to taking an annual plant that produces a fruit of interest, and grafting the top of the plant with roots from a perennial plant so that the grafted plant is able to produce the fruit of interest and live forever. In the case of B cells fused with immortal cells, the hybrid cell lines are known as hybridomas.

Scientists have long used hybridomas to produce antibody-based therapeutics that target specific antigens associated with disease. In this manner, therapeutics have been designed for conditions including cancer and several autoimmune diseases. The new challenge is to go one step further and make designer antibodies with more features, so that the patient receiving the antibody-based therapeutic treatment gets a bigger bang for their buck.

One avenue that is being explored is the engineering of more than one antigen site onto the same antibody molecule. In this way, two antigens that are believed to be associated with the same disease can be targeted to increase the chances of the antibody finding its target.

A more recent idea has been the continued engineering of two antigen targets onto one antibody molecule, but the new goal is to carefully choose the dual antibody targets in order to bring about a novel response in the body of the patient - only attainable via engineered co-engagement. Scientists purchased PBMCs from HemaCare to design experiments to this effect. Different antibody formats including whole molecules with engineered fragments were evaluated. A format designated as mAb-Fv - a far cry from that produced by B cells in the body - was deemed as the one that enabled simultaneous bivalent and monovalent co-engagement of distinct target engagements.

Research continues towards increasing the desired clinical response in patients with antibody therapeutics. Screening for antibodies that have higher starting affinities, greater pairing stability, or more tolerance to linkage at their N-termini, would be the next step for refinement of the antibody format. We at HemaCare are pleased to see our cells being used to aid this important research field and help improve the clinical efficacy of these antibodies.

Reference

[1] Gregory L. Moore, Cristina Bautista, Erik Pong et al., A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens. mAbs 3:6, 546-557; November/December 2011.

 

Topics: antibody therapeutics, B cells, Independent validation, PBMC

Daisy

Written by Daisy

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