Table 1 Clinic trials and patients characteristics
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 |