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Table 1 Clinic trials and patients characteristics

From: The efficacy and safety of anti-CD19/CD20 chimeric antigen receptor- T cells immunotherapy in relapsed or refractory B-cell malignancies:a meta-analysis

Study No. of patients Disease type Disease status Ag recognition moieties costimulatory domains CART generation Original T cell sources T cell culture time Transduction method T cell treatment CAR T cells persistence time Lymphodepletion IL-2 infusion to patients IL-2 infusion to cells The infused total cell number CAR T cells number Patients’ response
Kochenderfer, J. N. (2012) [13] 8 4: lymphoma 4: CLL Advanced, progressive CD19 CD28+ CD3ζ 2nd Autologous 24 days Gammaretrovirus OKT3 < 20 days, > 6 months Cyclophosphamide, fludarabine Yes 0.5–5.5 × 107 0.3–3.0× 107 5 PR
1 CR
1 SD
1 Died with influenza
Jensen, M. C. (2010) [34] 4 2: DLBCL
2: FL
Recurrent, refractory 2: CD20 2: CD19 CD3ζ 1st Autologous 106 days Electroporation OKT3, rHuIL-2 1 day-1 week BCNU TBI cytoxan, VP-16; Fludarabine NO; yes Yes 3–21 × 108; 40–60 × 108/m2 2 PD
1 Died
1 PR
Kochenderfer, J. N. (2013) [35] 10 4: CLL
4: MCL
2: DLBCL
Progressive CD19 CD28
CD3ζ
2nd Allogeneic 8 days Gammaretrovirus OKT3, IL-2 1 month No No Yes 1–10 × 106/Kg 0.4–7.8× 106/Kg 6 SD
2 PD
1 CR
1 PR
Brentjens, R. J. (2013) [36] 5 ALL Relapsed CD19 CD28
CD3ζ
2nd Autologous 14 days Gammaretrovirus CD3/CD28 beads 3–8 weeks Cyclophosphamide No 1.2–6.2 × 108 1.4–3.2×  108 5 CR
Till, B. G. (2012) [37] 3 2: MCL
1: FL
Relapsed, refractory CD20 CD28
CD3ζ
CD137 (4-1BB)
3rd Autologous >  69 days Electroporation OKT3, IL-2 12 months, 9 months Cyclophosphamide Yes 4.4 × 109/m2 1 PR
2 NE
Brentjens, R. J. (2011) [11] 9 8: CLL
1: ALL
Relapsed, refractory CD19 CD28
CD3ζ
2nd Autologous 11–18 days Retrovirus CD3/CD28 beads, CD19/CD80 artificial APCs 0 days, < 4 weeks, > 8 weeks No; Cyclophosphamide No Yes 1.0–11.1 × 109 1.4–32 × 108 3 NR
1 NE
2 PD
2 SD
1 PR
Cruz, C. R. (2013) [38] 8 6: ALL
2: CLL
Relapse CD19 CD28
CD3ζ
2nd Allogeneic 40 ± 12 days Retrovirus Irradiated LCLs, IL-2 1–12 weeks No Yes 1.9–11.3 × 107 3 CR
1 SD
1 PR
3 PD
Dai, H. (2015) [39] 9 ALL Relapsed, refractory CD19 4-1BB
CD3ζ
2nd Autologous; Allogeneic 10–12 days Lentivirus OKT3, IL-2 > 6 weeks, < 3–4 weeks C-MOAD; no No Yes 2.2–7.9 × 108 3 PD
2 CR
4 PR
Davila, M. L. (2014) [40] 16 ALL Relapsed, refractory CD19 CD28
CD3ζ
2nd Autologous 14 days Gammaretrovirus CD3/CD28 beads 2–3 months Cyclophosphamide No 3 × 106/kg 14 PR
2 NR
Savoldo, B. (2011) [28] 6 NHL Relapsed, refractory CD19 CD28
CD3ζ; CD3ζ
1st and 2nd Autologous 6–18 days Retrovirus OKT3, IL-2 4–6 weeks; < 6 weeks No Yes 2–20 × 107/m2 4 PD
2 SD
Kochenderfer, J. N. (2015) [32] 15 9: DLBCL
2: lymphoma
4: CLL
Relapsed, refractory CD19 CD28
CD3ζ
2nd Autologous 10 days Gammaretrovirus OKT3, IL-2 35- > 75 days Cyclophosphamide, fludarabin No Yes 1–5 × 106/kg 8 CR
4 PD
1 SD
2 NE
Maude, S. L. (2014) [41] 30 ALL Relapsed, refractory CD19 4-1BB
CD3ζ
2nd Autologous 12 days Lentivirus CD3/CD28 beads >  11 months 3: no
15: Flu/Cy
5: Cy/VP
3: Cy
2: CVAD
1: Clofarabine
1: Etoposide/Cytarabine
No 0.3–9.58 × 108 27 CR
3 NR
Porter, D. L. (2015) [26] 14 CLL Relapsed, refractory CD19 4-1BB
CD3ζ
2nd Autologous 10–12 days Lentivirus CD3/CD28 beads 1–12 months 3: fludarabine/cyclophosphamide
5: pentostatin/cyclophosphamide
6: bendamustine
No 0.14–11 × 108 4 CR
4 PR
6 NR
Wang, Y. (2014) [42] 7 DLBCL Refractory CD20 CD137
CD3ζ
2nd Autologous 10–12 days Lentivirus > 90 days Cyclophosphamide, Vincristine, Etoposide, Dexamethasone, Doxorubicin, Methylprednisolone, Carboplatin, cytosine, arabinoside; NO No 1–6 × 107/kg 0.2–2.2 × 107/kg 1 CR
1 Died of massive hemorrhage
of alimentary tract
4 PR
1 PD
Kochenderfer, J. N. (2010) [43] 1 FL Progressive CD19 CD28, CD3ζ 2nd Autologous 18 days Retrovirus IL-2, OKT3 27 weeks Cyclophosphamide, fludarabin Yes Yes 4× 108 PR
Wang, X. (2016) [44] 16 7: DLBCL
1: MCL;
4: DLBCL
4: MCL
Relapse CD19 CD3ζ; CD28
CD3ζ
1st; 2nd Autologous 7–19 days Lentivirus CD3/CD28 beads, IL-2, IL-15 18.25 days; 20.5 days No Yes 2.5–10× 107; 5–20× 107 5 CR
2 PR
1 PD;
8 CR
Lee, D. W. (2015) [31] 21 20: ALL 1: NHL Relapsed
refractory
CD19 CD28, CD3ζ 2nd Autologous 11 days Retrovirus CD3/CD28 beads 68 days Fludarabine, cyclophosphamide No No 0.03–3× 106/kg 14 CR
4 PD
3 SD
Kalos, M. (2011) [12] 3 CLL Relapsed
refractory
CD19 CD137
CD3ζ
2nd Autologous 10 days Lentivirus CD3/CD28 beads ≥ 6 months Bendamustine, rituximab, Pentostatin, cyclophosphamide No No 0.14–11× 108 2 CR
1 PR
  1. When counted the infusion cell number, the patients’ weight were identified as 50 Kg on average, and patients’ body surface area were identified as 1.8 on average
  2. ALL: acute lymphocytic leukemia; CLL: chronic lymphocytic leukemia; FL: follicular lymphoma; MCL: mantle cell lymphoma; DLBCL: diffuse large B-cell lymphoma; NHL: non-Hodgkon’s lymphoma
  3. LCLs: EBV-transformed lymphoblastoid B-cell lines
  4. CR: complete response; PR: partial response; SD: stable disease; PD: progress disease; NR: no response; NE: not evaluate