Crescendo announces the Crescendo Mouse
Technology generates superior human single domain antibody VH fragments in a transgenic mouse
Crescendo Biologics Limited announces the Crescendo Mouse, an antibody fragment technology which allows the generation of human single domain antibody VH fragments from a transgenic mouse.
VH fragments are antibody-based therapeutic proteins that have applications beyond the scope of full length antibodies. They are the smallest antibody fragments that retain the ability to bind antigens specifically and with highaffinity and, when generated in the Crescendo Mouse, human VH have biophysical properties that make them attractive drug products. VH fragments can be formulated for topical delivery, are amenable to modular engineering of bispecific and multivalent products, have tissue penetration characteristics, and are simple to manufacture in microbial systems.
Key to generation of VH fragments in the mouse is Crescendo’s triple knock out (TKO) background, which is completely devoid of all endogenous immunoglobulin chains, and therefore enables in vivo maturation of human VH single domains uncontaminated by association with any light chains. B cell development within the Crescendo Mouse is driven from a construct introduced into the TKO background that combines human V- D- and J- genes, together with murine constant and regulatory regions, to generate heavy chain only antibodies. The power of the mouse immune system is consequently fully harnessed to drive B cell development and maturation, leading to a repertoire of fully-human VH domains with stability and solubility.
The Crescendo Mouse responds to immunisation with target proteins and in vivo B cell maturation yields diverse human VH domains, from all VH families, which have also undergone somatic hypermutation. Because the antibody response following immunisation is entirely encompassed within the VH domain, Crescendo has been able to develop a integrated discovery process utilising in vitro display to mine and identify VH drug candidates from immunised mice. Purified VH fragments have been shown to bind immunogen with affinity, exhibit thermostability and have expression levels. These data indicate that B cell maturation in the Crescendo Mouse is driving selection and optimisation of matured human VH domains, with all of the properties that make them potent, drug quality antibody-based therapeutics.
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Topic world Antibodies
Antibodies are specialized molecules of our immune system that can specifically recognize and neutralize pathogens or foreign substances. Antibody research in biotech and pharma has recognized this natural defense potential and is working intensively to make it therapeutically useful. From monoclonal antibodies used against cancer or autoimmune diseases to antibody-drug conjugates that specifically transport drugs to disease cells - the possibilities are enormous
