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- Title
convertibleCARs: A chimeric antigen receptor system for flexible control of activity and antigen targeting.
- Authors
Landgraf, Kyle E.; Williams, Steven R.; Steiger, Daniel; Gebhart, Dana; Lok, Stephen; Martin, David W.; Roybal, Kole T.; Kim, Kaman Chan
- 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 convertibleCARTM-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 (MicAbodyTM). Efficacy against Raji tumors in NSG mice was dependent upon doses of both a rituximab-based MicAbody and convertibleCAR-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 convertibleCAR-T cells in vitro and in vivo. By altering the Fv domains of the MicAbody or the payload fused to the orthogonal ligand, convertibleCAR-T cells can be readily targeted or regulated. Landgraf et al. developed a chimeric antigen receptor (CAR) platform that functions as a modular system. convertibleTM-T cells are designed to kill antigen-expressing target cells only in the presence of ligands fused to antigen-targeting antibodies (MicAbodyTM). This method provides a wide dosing window while minimizing toxicity.
- Subjects
T cells; CHIMERIC antigen receptors; ANTIGEN analysis; RECEPTOR-ligand complexes; RITUXIMAB
- Publication
Communications Biology, 2020, Vol 3, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-020-1021-2