Synthetic Biology Parts, Devices and Applications

(Nandana) #1

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
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