The multi-specific V-based Humabody CB213 co-targets PD1 and LAG3 on T cells to promote anti-tumour activity.

Background: Improving cancer immunotherapy long-term clinical benefit is a major priority. It has become apparent that multiple axes of immune suppression restrain the capacity of T cells to provide anti-tumour activity including signalling through PD1/PD-L1 and LAG3/MHC-II.

Methods: CB213 has been developed as a fully human PD1/LAG3 co-targeting multi-specific Humabody composed of linked V domains that avidly bind and block PD1 and LAG3 on dual-positive T cells.

Stress selections on domain antibodies: 'what doesn't kill you makes you stronger'.

In addition to the desired specificity and affinity for their respective therapeutic targets, antibody-based drugs must also demonstrate an ability to be manufactured and formulated at the concentrations needed for therapeutic application and to remain resistant to aggregation during storage to reduce the risk of induced immunogenicity. Improvements to the thermodynamic stability of the folded state of the protein are considered to be critical for decreasing the aggregation propensity of the protein. In this work, we have improved the biophysical properties of a number of human domain antibodies (dAbs) by identifying mutations which decrease the propensity for dAb self-aggregation without compromising the affinity for their respective target antigen.

Next generation immunotherapeutics--honing the magic bullet.

Most therapeutic antibodies in the clinic today are based on fully humanised immunoglobulins. They have proven to be outstandingly effective, especially for the treatment of cancer, autoimmune and inflammatory diseases where the target is a single, well-defined and accessible molecule. Many diseases however are complex, involving multiple mediators or signalling pathways that could be targeted simultaneously to maximise clinical benefit.

Engineering high affinity superantigens by phage display.

Protein L (PpL) is a B-cell superantigen from Peptostreptococcus magnus known to bind to mammalian Vkappa light chains. PpL from P.magnus strain 312 comprises five homologous immunoglobulin (Ig) binding domains.

The use of recombinant antibodies in proteomics.

Recombinant antibodies are becoming increasingly important in the field of proteomics. Recent advances include the development of large phage-antibody libraries that contain high-affinity binders to almost any target protein, and new methods for high-throughput selection of antibody-antigen interactions. Coupled with a range of new screening technologies that use high-density antibody arrays to identify differentially expressed proteins, these antibody libraries can be applied to whole proteome analysis.