Synthetic Biology Parts, Devices and Applications

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