Table 1.
Structure and features of every generation of CAR-T
| Structure of CAR | First-generation CAR | Second-generation CAR | Third-generation CAR | Next-generation CAR | Universal CAR | |
|---|---|---|---|---|---|---|
| Similarities | An extracellular antigen-recognition region consisting of an scFv | |||||
| A flexible hinge region derived from a CD8 molecule or CD28 or Fc region of an antibody | ||||||
| A transmembrane derived from CD8 or CD28 | ||||||
| Differences | Intracellular domain | only CD3ζ | CD3ζ | CD3ζ | CD3ζ | CD3ζ |
| One costimulatory molecule: CD28 or 4-1BB | ≥ 2 Costimulatory molecules: CD28, 4-1BB, ICOS or OX40 | One costimulatory molecule: CD28 or 4-1BB | One costimulatory molecule: CD28 or 4-1BB | |||
| Functional elements: interleukins, chemokine receptors, on-off-switches or suicide genes etc. | Knock-out of TCRs or/and HLAs | |||||
| In vivo Persistence | Low (days to 2 months) | Imporved (3 months to years) | Not superior to 2nd-generation | Exploration | Exploration | |
| Antitumor Effects | Low (ORR 0–40%) | Imporved (ORR depending on the tumor type) | Not superior to second-generation | Exploration | Exploration | |