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

Commun Biol. 2020 Jun 9;3(1):296. doi: 10.1038/s42003-020-1021-2.


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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / immunology*
  • Apoptosis
  • Cell Proliferation
  • Female
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interleukin-2 / genetics
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mutation*
  • NK Cell Lectin-Like Receptor Subfamily K / genetics
  • NK Cell Lectin-Like Receptor Subfamily K / immunology*
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / immunology*
  • Sequence Homology
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Histocompatibility Antigens Class I
  • IL2 protein, human
  • Interleukin-2
  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Chimeric Antigen