354 17 Synthetic Biology in Immunotherapy and Stem Cell Therapy Engineering
ζ
ζ
ζ
ζ
T-cell
membrane
Antigen-binding
domain
(e.g., scFv)
Extracellular
spacer domain
Transmembrane
domain
Activation signaling
(a) domain (e.g., CD3ζ)
Costimulatory domain(s)
(e.g., CD28, 4-1BB, etc.)
First
generation
Second
generation
Third
generation
(b) T-cell activation (c)
T-cell
membrane
Target-cell
Antigen membrane
A OR B
Inhibitory
ζ domain
CAR A
No T-cell activation
iCAR B
Antigen
A NOT B
ζ ζ
A/B OR-gate
CAR
(d) (e)
ζ
CAR A CCR B
T-cell activation
Antigen
A AND B
ζ
T-cell
membrane
Target-cell
membrane
CAR
part II
CAR
part I
T-cell activation
Antigen
AND rapalog
Heterodimerization
Rapalog domains
(f)
T-cell
membrane
Target-cell
membrane
CAR
T-cell activation
synNotch
receptor
CAR
ζ
gamma
secretase
TF
Nucleus
Antigen
A AND (Then) B
CAR expression