Work

convertibleCARs: A chimeric antigen receptor system for flexible control of activity and antigen targeting

Year: 2020

Type: article

Abstract: We have developed a chimeric antigen receptor (CAR) platform that functions as a modular system to address limitations of traditional CAR therapies. An inert form of the human NKG2D extracellular domain (iNKG2D) was engineered as the ectodomain of the CAR to generate convertible CAR TM -T cells. These cells were specifically directed to kill antigen-expressing target cells only in the presence of an activating bispecific adapter comprised of an iNKG2D-exclusive ULBP2-based ligand fused to an antigen-targeting antibody (MicAbody TM ). Efficacy against Raji tumors in NSG mice was dependent upon doses of both a rituximab-based MicAbody and convertible CAR-T cells. We have also demonstrated that the exclusive ligand-receptor partnering enabled the targeted delivery of a mutant form of IL-2 to selectively promote the expansion of convertible CAR-T cells in vitro and in vivo. By altering the Fv domains of the MicAbody or the payload fused to the orthogonal ligand, convertible CAR-T cells can be readily targeted or regulated.

Source: Communications Biology

DOI: 10.1038/s42003-020-1021-2