EVALUATION OF NOVEL ANTIBODIES FOR CHIMERIC ANTIGEN RECEPTOR T CELL APPLICATIONS

Abstract

While chimeric antigen receptor (CAR) T cells have seen recent clinical success, there are still major challenges in expanding this class of therapeutics clinically. In part, this is due to a lack of feasible targets, limiting CAR T cells to a handful of targets under current clinical investigation.

This thesis will outline the creation of a CAR development platform for the conversion of monoclonal antibodies (mAbs) into candidate CAR constructs. This platform is capable of rapidly selecting for optimal CAR construct design, rejecting non-efficacious CARs at an early stage, allowing an efficient means of evaluating large numbers of candidate CARs. Of the candidates tested in this thesis, CAR(2448) and CAR(GR6D11) T cells show promise against Annexin A2 and CEACAM6-positive cancers respectively.

The CAR development platform outlined in this thesis fills a gap in the developmental process of CAR T cells, shortening the time required to optimise novel CAR candidates.