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Table 1 Summary of costimulatory molecules in CAR T cell trials for solid tumors

From: Gene modification strategies for next-generation CAR T cells against solid cancers

Costimulatory molecules

Functional characteristics

CAR target antigen

Malignancy

Clinical trials

Phase

Status

Enrolled patients

Sponsor

CD28

Increased cytokine production;

more potent effector function;

more rapid T cell proliferation and tumor elimination [43]

Lewis Y

Advanced solid cancer

NCT03851146

I

Recruiting

30

Peter MacCallum Cancer Centre

Chlorotoxin

Glioma

NCT04214392

I

Recruiting

36

City of Hope Medical Center

HER2

Sarcoma

NCT00902044

I

Active, not recruiting

36

Baylor College of Medicine

 

Glioblastoma

NCT01109095

I

Completed

16

Baylor College of Medicine

4-1BB

Greater persistence;

increased central memory T cell generation [43]

PSCA

Prostate cancer

NCT03873805

I

Recruiting

33

City of Hope Medical Center

PD-L1

Lung cancer

NCT03330834

I

Recruiting

22

Sun Yat-sen University

Mesothelin

Pancreatic cancer

NCT03638193

I

Recruiting

10

Shenzhen BinDeBio Ltd.

 

MPM

NCT01355965

I

Completed

18

University of Pennsylvania

 

Ovarian cancer

NCT02159716

I

Completed

19

University of Pennsylvania

GPC3

Hepatocellular cancer

NCT02715362

I/II

Recruiting

30

Shanghai GeneChem Co Ltd.

IL13Ralpha2

Melanoma

NCT04119024

I

Recruiting

24

Jonsson Comprehensive Cancer Center

 

Glioblastoma

NCT04003649

I

Recruiting

60

City of Hope Medical Center

CEA

Liver metastases

NCT02862704

I/II

Recruiting

20

Xijing Hospital

CD171

Neuroblastoma

NCT02311621

I

Recruiting

40

Seattle Children’s Hospital

MET

Melanoma

NCT03060356

I

Terminated

77

University of Pennsylvania

 

Breast cancer

NCT03060356

I

Terminated

77

University of Pennsylvania

EGFRvIII

Glioblastoma

NCT03726515

I

Active, not recruiting

7

University of Pennsylvania

CD28 and 4-1BB

Strong PI3Kinase/Akt activation;

reduced apoptosis of CD8+ T cells;

enhanced effector function of CD8+ T cells [46]

CD171

Neuroblastoma

NCT02311621

I

Recruiting

40

Seattle Children's Hospital

CD28 and OX40

CD28-OX40-CD3ζ CAR increased the production of IL-2 and IL-10;

CD28-CD3ζ-OX40 CAR decreased the production of IL-2 and IL-10 [39, 47]

GD2

Neuroblastoma

NCT01822652

I

Active, not recruiting

11

Baylor College of Medicine

Sarcoma

NCT01953900

I

Active, not recruiting

26

Baylor College of Medicine

  1. CAR chimeric antigen receptor, HER2 human epidermal growth factor receptor-2, PSCA prostate stem cell antigen, GPC3 glypican-3, CEA carcinoembryonic antigen, MET mesenchymal to epithelial transition factor, EGFRvIII epidermal growth factor receptor variant III, MPM malignant pleural mesothelioma, GD2 disialoganglioside2