Key points: Introduction to CAR-T cells

  • Ordinarily, T cells can only recognise fragments of peptides presented by other cells bound to a major histocompatibility complex (MHC) molecule. Antibodies can bind to much larger molecules but cannot kill targets directly.
  • Chimeric antigen receptor (CAR) T cells combine the antigen recognition capabilities of an antibody with the direct killing machinery of a T cell.
  • Gene transfer is achieved using modified retroviruses. The CAR is encoded by a single gene to make this transfer possible.
  • To be activated, T cells require two signals: the first is produced through antigen–TCR binding, the second through the interactions of co-stimulatory molecules. The incorporation of co-stimulatory molecules into the CAR construct allows delivery of both signal 1 and signal 2 to the T cell by TCR–antigen binding only. 
  • Second-generation CAR-T cells, which incorporate this co-stimulatory domain, are the first truly effective CAR-T cells.
  • CAR-T cells in current clinical use target the B cell antigen CD19, but it is possible to design CAR-T cells against many targets.