Teams from Charles River and Distributed Bio presented research at AACR 2021 in April detailing how their technology and expertise benefits CAR T cell therapy developers.
Distributed Bio’s phage-display libraries (SuperHuman 2.0 and Tungsten) have been designed to be biophysically stable and non-immunogenic. Their size and clonal diversity, coupled with the use of streamlined work-flows, enable the rapid identification of large panels of sequence-unique binders which can then be assessed for CAR suitability by exploiting the integrated approach offered by Distrbuted Bio’s partnership with Charles River, they explained.
Inherent risks in CAR-T therapy development
Outlining how the global market for chimeric antigen receptors (CAR) therapy is continuing to grow rapidly, with many clinical success stories for B-cell malignancies, the experts noted how the path to clinical success has not been smooth, however, with early reports of organ damage and even deaths following CAR T cell therapy, highlighting the significant risks involved in the development of such treatment approaches.
There is a clear requirement to understand and mitigate the underlying mechanisms that result in unwanted toxicities, said the Charles River and Distributed Bio teams.
Off-target binding and tonic signaling are indicated in many pre-clinical and clinical cell therapy failures, and it is becoming increasingly apparent that CAR design – particularly the selection of the tumor targeting moiety with exquisite specificity, desirable biophysical attributes and appropriate affinity – is key to developing a successful therapy, said Katherine Vousden, Science Director, large molecules, at Charles River Laboratories.