Target deconvolution success for MedImmune

Cell preparation for Retrogenix off-target screening of biotherapeutics

A target deconvolution project undertaken by Retrogenix has revealed the identity of a promising target for cancer immunotherapy that has been uncovered by scientists at MedImmune and Cambridge University. The results have just been published in the journal, Oncotarget.

The project aimed to identify new cancer immunotherapy targets by phenotypic screening on human regulatory T (Treg) cells. Phage display using designed ankyrin repeat proteins (DARPins) was employed to select antibody-like molecules that showed preferential binding to Treg cells. Rapid target deconvolution using the Retrogenix technology identified TNFR2 as the primary receptor for all molecules screened. Subsequent tests on specific molecules that were identified as TNFR2-agonists resulted in tumour inhibition in mouse models, highlighting the importance of TNFR2 as an immunotherapy target.

This paper, which is the second recent phenotypic screening and target deconvolution success story from MedImmune, once again points to the utility of target-agnostic screening in drug discovery.

The full paper, by Geoffrey Williams et al., is available as an early on-line open-access publication.

If you would like to talk to a member of our science team about target deconvolution, receptor identification or off-target profiling then please do get in touch.