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Table 1 Summary and comparison of four generations of CAR-T therapy

From: Advances on chimeric antigen receptor-modified T-cell therapy for oncotherapy

CAR generations

Signal domain

Target antigen

Associated diseases

Profile

References

1st

 

CD3ζ

TAG72

Metastatic colorectal cancer

Limited persistence

[84]

 

CD3ζ

FRα

Ovarian cancer

Limited persistence

[26]

 

CD3ζ

L1-CAM

Metastatic neuroblastoma

Limited persistence

[85]

2nd

 

CD3ζ + CD28/CD137 (41BB)

CD19

B cell lymphomas

Enhanced expansion, persistence and anti-tumor effect

[28, 40, 86, 87]

 

CD3ζ + 41BB(CD137)

IL13Rα2

GBM

Improved anti-tumor activity and T cell persistence

[22]

 

CD3ζ + 41BB (CD137)

FRα

Ovarian cancer

Augmented cytokine secretion and proliferation

[88]

3rd

 

CD3ζ + CD28 + 41BB(CD137)

CD19

ALL

Superior activation and proliferation capacity

[89]

 

CD3ζ + CD28 + 41BB(CD137)

PMSA

–

Promoted cytokine release, T-cell survival and tumor elimination

[90]

 

CD3ζ + CD28 + CD137 (41BB)

Mesothelin

Mesothelioma

Prolonged persistence

[30]

 

CD3ζ + CD28 + 41BB(CD137)

CD22

ALL

Inferior antileukemic activity

[32]

4th

 

CD3ζ + iIL-12+ co-stimulator

CEA

CEA+ tumors

Improved antitumor efficacy

[35]

  1. TAG72 tumor-associated glycoprotein 72, CEA carcinoembryonic antigen, IL13Rα2 IL-13 receptor α2, FRα folate receptor-α, L1-CAM L1-cell adhesion molecule, PSMA prostate-specific membrane antigen