Table 2 Multispecific CAR-T cell therapy in hematological tumors

B-NHL

Phase 1 (NCT03233854)

CD19/CD22

Adult, Older Adult

21

1-Sep-17

Stanford University, School of Medicine; Palo Alto, California, United States

4-1BB-CD3ζ

6CR

3 ×  10⁶

CRS gr. 3–4 (5%), Neurotoxicity gr.3–4 (0%)

[47]

Phase 2 (NCT03196830)

CD19/CD22

Child, Adult, Older Adult

32

1-Jun-17

the First Affiliated Hospital of Soochow University the First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

4-1BB-CD3ζ

11CR

a total dose of 3.690×  10⁸–3.285×  10⁹

CRS gr. 3–4 (28%), Neurotoxicity gr.3–4 (12.5%)

[48]

Phase 1 (ChiCTR1800015575)

CD19/CD22

Child, Adult, Older Adult

16

10-Apr-18

the First Affiliated Hospital, School of Medicine, Zhejiang University

4-1BB-CD3ζ

10CR

1–10× 10⁶

CRS gr. 3–4 (6%), Neurotoxicity gr.3–4 (0%)

[49]

Phase 1/2 (NCT03097770)

CD19/CD20

Child, Adult, Older Adult

87

1-Apr-17

Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital Beijing, Beijing, China

4-1BB-CD3ζ

61CR

0.5× 10⁶–8× 10⁶

CRS gr. 3–4 (10%), Neurotoxicity gr.3–4 (2%)

[50]

Phase 1 (NCT03019055)

CD19/CD20

Adult, Older Adult

19

16-Oct-17

Froedtert Hospital & Medical College of Wisconsin, Milwaukee, Wisconsin, United States

4-1BB-CD3ζ

12CR

2.5 ×  10⁵–2.5× 10⁶

unknown

[51]

CD19/CD70,CD19/20/22,CD19/CD37

[421,422,423]

B-ALL

Phase 1 (ChiCTR1800015575)

CD19/CD22

Child, Adult, Older Adult

15

10-Apr-18

the First Affiliated Hospital, School of Medicine, Zhejiang University

4-1BB-CD3ζ

13CR

1.04× 10⁶–7.02× 10⁶

CRS gr. 3–4 (13%), Neurotoxicity gr.3–4 (0%)

[89]

Phase 1 (NCT03233854)

CD19/CD22

Adult, Older Adult

17

1-Sep-17

Stanford University, School of Medicine, Palo Alto, California, United States

4-1BB-CD3ζ

15CR

3× 10⁶

CRS gr. 3–4 (6%), Neurotoxicity gr.3–4 (18%)

[47]

Phase 1 (NCT03185494)

CD19/CD22

Child, Adult, Older Adult

6

1-Aug-17

Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital Beijing, Beijing, China

4-1BB-CD3ζ

6CR

1.7× 10⁶–3×  10⁶

CRS gr. 3–4 (0%), Neurotoxicity gr.3–4 (0%)

[87]

Phase 1 (NCT03289455)

CD19/CD22

Child, Adult

15

26-Jun-17

Great Ormond Street Hospital for Children NHS Foundation Trust London, United Kingdom; University College London Hospitals NHS Foundation Trust

London, United Kingdom; Royal Manchester Children’s Hospital

Manchester, United Kingdom

4-1BB-CD3ζ

13CR

0.3–2× 10⁶,3 × 10⁶,4.3–5×  10⁶

CRS gr. 3–4(0%), Neurotoxicity gr.3–4 (7%)

[424]

Phase 1 (ChiCTR-ONC-17013648)

CD19/CD22

Child, Adult

21

4-Dec-17

Beijing Boren Hospital, Beijing, China

4-1BB-CD3ζ

14CR

0.486–5.0× 10⁵ (CD19), 0.32–5.0× 10⁵ (CD22)

CRS gr. 3–4 (0%), Neurotoxicity gr.3–4 (0%)

[86]

CD20/CD22,CD19/CD123,CD19/BAFF-R

[82, 425, 426]

T-ALL

CD5/CD7

[66]

AML

CD123/CD19,FLT3/NKG2DL,CD123/CLL1,CD13/TIM3,CD123/FRβ

[427,428,429,430,431]

CLL

Phase 1 (NCT03019055)

CD19/CD20

Adult, Older Adult

3

16-Oct-17

Froedtert Hospital & Medical College of Wisconsin, Milwaukee, Wisconsin, United States

4-1BB-CD3ζ

2CR

2.5 × 10⁵–2.5×  10⁶

unknown

[51]

MM

Phase 1 (ChiCTR1800018143)

BCMA/CD38

Adult, Older Adult

23

1-Sep-18

Institute of Hematology, Union Hospital Affiliated to Tongji Medical College, Huazhong University of science and technology

4-1BB-CD3ζ

12CR

0.5,1.0,2.0,3.0 and 4.0× 10⁶

CRS gr. 3–4 (22%), Neurotoxicity gr.3–4 (0%)

[169]

Phase 2 (ChiCTR1800017051)

BCMA/CD38

Adult, Older Adult

22

1-Jun-18

The first central hospital of Tianjin, Tianjin, China

4-1BB-CD3ζ

12CR

2× 10⁶ (BCMA), 2×  10⁶ (CD38)

CRS gr. 3–4 (27%), Neurotoxicity gr.3–4 (0%)

[170]

Phase 2 (ChiCTR-OIC-17011272)

BCMA/CD19

Adult, Older Adult

62

1-May-17

The Affiliated Hospital of Xuzhou Medical University, Jiangsu, China

4-1BB-CD3ζ

37CR

1× 10⁶ (BCMA), 1×  10⁶ (CD19)

CRS gr. 3–4 (10%), Neurotoxicity gr.3–4 (3%)

[171]