SOUTH SAN FRANCISCO, Calif., Feb. 5, 2018 /PRNewswire/ -- GigaGen Inc., a biopharmaceutical company developing a pipeline of novel antibody therapies, has published a study in collaboration with authors from a leading antibody drug developer that sheds new light on methods for increasing the success of antibody discovery in mice. The study, "A natively paired antibody library yields drug leads with higher sensitivity and specificity than a randomly paired antibody library," is available online and will appear in the upcoming issue of the peer-reviewed scientific journal mAbs.
The study was the first to rigorously compare antibody discovery from natively paired antibody libraries to those from randomly paired libraries, with the goal of determining which approach would result in antibodies with the best characteristics for development. The results hold relevancy for pharmaceutical and biotechnology companies that are mining antibodies for therapeutic development.
"We know that better antibody discovery will lead to better antibody therapies, and that was the driving force of this study," said David Johnson, Ph.D., CEO of GigaGen and senior author on the publication. "Prior antibody discovery methods do not capture high-potential antibodies with enough efficiency to bring new therapeutics to patients in a timely manner, and that is preventing drug developers from capitalizing on an increasing understanding of disease biology."
In the study, GigaGen and its collaborators used interleukin 21 receptor (IL-21R) as a test immunogen, as this target protein is implicated in a wide range of inflammatory diseases and other immune-related disorders. After immunizing humanized mice and extracting B cells, researchers embarked on two different methods of antibody discovery and library creation. One approach was a conventional random-pairing method. The other method, developed by GigaGen, achieves native pairing using droplet microfluidics.
Antibodies with native pairing have the same protein structure as those that occur naturally in the body – with the heavy chain of the antibody paired to the light chain as it would occur in nature. Antibodies with random pairing are artificially derived from antibody discovery methods that randomly match a light chain with a heavy chain, and therefore for the most part do not occur naturally. Researchers have long believed that natively paired antibodies hold better therapeutic potential with fewer side effects because they have already been proven in nature.
"We found that the natively paired method is more sensitive and specific than the random pairing method," Dr. Johnson said, noting that using both methods concurrently helps generate additional antibody diversity that might be valuable for downstream development. "The randomly paired method failed to identify nearly half of the true natively paired binders, suggesting lower sensitivity, and the problem with missing these natively paired binders is that one winds up wasting precious time and resources on drug candidates that may be less effective."
GigaGen's natively paired discovery method, known commercially as Surge, leverages best-in-class microfluidics, genomics, and protein library engineering to identify antibodies as they occur in nature. The method revolutionizes key bottlenecks of drug discovery and development by enabling ultra-fast drug candidate identification and informing drug target selection by profiling millions of cellular interactions in an immune response. GigaGen is using the method to understand immune dysregulation and develop novel antibody therapies for oncology and immune deficiency indications.
About GigaGen GigaGen is a privately-held, preclinical biopharmaceutical company developing novel antibody therapies to treat diseases of immune dysregulation. GigaGen's deep understanding of immune dysregulation is enabled by industry-leading technology that quickly captures the genetic makeup of entire immune repertoires to analyze B cells at a rate of millions per hour, while simultaneously identifying their antigen and protein binders. GigaGen has a robust internal pipeline consisting of novel antibodies against immuno-oncology targets, in addition to the first recombinant intravenous immunoglobulin (IVIG) for patients with immune deficiency. For more information visit www.GigaGen.com.