Design of chimeric antigen receptors with integrated controllable transient functions

Sci Rep. 2016 Jan 11:6:18950. doi: 10.1038/srep18950.

Abstract

The ability to control T cells engineered to permanently express chimeric antigen receptors (CARs) is a key feature to improve safety. Here, we describe the development of a new CAR architecture with an integrated switch-on system that permits to control the CAR T-cell function. This system offers the advantage of a transient CAR T-cell for safety while letting open the possibility of multiple cytotoxicity cycles using a small molecule drug.

MeSH terms

  • CD8 Antigens / genetics
  • CD8 Antigens / immunology
  • Cell Line, Tumor
  • Coculture Techniques
  • Cytotoxicity, Immunologic / drug effects*
  • Gene Expression
  • Genetic Engineering / methods*
  • Genetic Vectors / chemistry
  • Genetic Vectors / immunology
  • Humans
  • Mutant Chimeric Proteins / genetics*
  • Mutant Chimeric Proteins / immunology
  • Protein Domains
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • Single-Chain Antibodies / genetics
  • Sirolimus / analogs & derivatives
  • Sirolimus / pharmacology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tacrolimus / pharmacology
  • Transfection

Substances

  • AP 21967
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Mutant Chimeric Proteins
  • Receptors, Antigen, T-Cell
  • Single-Chain Antibodies
  • Sirolimus
  • Tacrolimus