Monoclonal antibodies are among the most successful class of biological therapeutics currently available.
Their unique appeal lies both in their specificity (i.e., their capacity to engage disease associated molecules in a highly discriminating fashion), superior safety profiles and their ability to marshal the might of the body’s immune system against target molecules, cells or pathogens. Today, scores of monoclonal antibodies are approved for the treatment of diverse conditions from cancer to infectious diseases, and hundreds more are at various stages of development.
The Trianni Mouse Platform offers scientists easy-to-apply monoclonal antibody discovery optimized for the isolation of best-in-class humanized therapeutic candidates. Scientists benefit from a similar route to high quality fully human antibody genes.
With the right platform, antibodies are easy to isolate — the immune system generates a library of billions of different antibodies, each antibody with a unique specificity. To isolate attractive leads, scientists expose a host to the antigen of interest and then screen for binding and/or function. Genetically-engineered mice now act as robust engines for the generation of diverse repertoires of affinity-matured, fully-human variable regions with intrinsic drug-like properties necessary for successful development including high potency, specificity, manufacturability, solubility and low risk of immunogenicity. Few existing or contemplated human transgenic mouse platforms express a full human antibody repertoire. The Trianni Mouse is the only one to do so in a single organism. This approach guarantees efficient expression of the full human antibody repertoire and at the same time maintains the natural immune response of the wild-type mouse, allowing researchers to exploit advantages in terms of efficiency in drug discovery and development. Several Trianni Mouse-derived antibodies are currently in development.
The Trianni Mouse carries extensively engineered versions of all three antibody-encoding genetic loci (Heavy, Kappa, and Lambda). The normal mouse variable and diversity/joining gene segments in these loci have been replaced by synthetic chimeric versions each comprised of human coding sequences combined with mouse regulatory genomic sequences. The Trianni Mouse loci are optimized for the expression of antibodies that are entirely human in their variable parts yet completely permissive of efficient lymphocyte development and immune responses in the mouse because they retain mouse constant domains. Fully human therapeutics can be generated from such chimeric antibodies by standard single-step cloning methodology.
THE TRIANNI MOUSE DIFFERENCE
The V gene segments in the Trianni Mouse are chimeric. However, the V regions of the antibodies that the mouse synthesizes are entirely human.
Antibodies that are optimized for function in the mouse yet express a full repertoire of human variable domains.