Table 1. . Chimeric antigen receptor-T therapy trials in adults with B-cell malignancy.
| Study (year) | Study center | Patient number | Patient population | Infused CART- celldose | CAR construct and signaling/(generation) | Origin type of the CAR T cells (autologous vs allogeneic) | Conditioning chemotherapy | Complete remission | Partial remission | Stable disease | Progressive disease |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Brentjens et al. (2011) | MSKCC | 8 | Refractory CLL8 | 3 × 106, to 1–3 × 107 T cells/kg | scFv-CD28-CD3ζ (2nd generation) (anti-CD19) |
Autologous | Cyclophosphamide | 2 CLL | 5 CLL | ||
| Kochenderfer et al. (2012) | NCI | 8 | B-cell lymphoma: Follicular 3, CLL 4, Splenic marginal zone lymphoma 1 |
0.3 × 107 to 3.0 × 107CAR T cells/kg |
scFv-CD28-CD3ζ (2nd generation) (anti-CD19) |
Autologous | Cyclophosphamide, fludarabine | 1 CLL = 1 |
6 CLL = 2 Lym = 4 |
1 CLL = 1 |
|
| Brudno et al (2016) | NCI | 20 | 5 CLL 5DLBCL 5 ALL 5 MCL (mantle celllymphoma) |
0.4–8.2 × 106 cells/kg | scFv-CD28-CD3ζ (2nd generation) (anti-CD19) |
Allogenic | Cyclophosphamide, fludarabine | 6 CLL = 1 ALL = 4 Lym = 1 |
2 CLL = 1 Lym = 1 |
8 CLL = 1 Lym = 7 |
4 CLL = 2 ALL = 1 Lym = 1 |
| Kochenderfer (2015) | NCI | 13 | 5-DLBCL 4-PMBCL, 1-NHL 3-chronic lymphocytic leukemia |
1–5 × 106 cells/kg | scFv-CD28-CD3ζ (2nd generation) (anti-CD19) |
Autologous | Bendamustine 1 Bendamustine/Rituximab 1 Pentostatin/Cyclophosphamide1 | 7 CLL = 2 Lym = 5 |
3 CLL = 1 Lym = 2 |
1 Lymp | |
| Kalos et al. (2011) | UPENN | 3 | Chemotherapy- resistantCLL | 1.1–5.8 × 109 cells/kg | scFv-CD-137- CD3ζ (2nd generation) (anti-CD19) |
Autologous | Cyclophosphamide, Fludarabine, Vincristine Etoposide, methotrexate, cytarabine and adriamycin | 2 CLL = 2 |
1 CLL = 1 |
||
| Maude et al. (2014) | UPENN | 5 | Relapsed ALL | 0.76 × 106 to 20.6 × 106 CTL019 cells/kg |
scFv-CD-137- CD3ζ (2nd generation) (anti-CD19) |
Autologous | Fludarabine/cyclophosphamide 3, pentostatin/cyclophosphamide 5, bendamustine 6 | 5 ALL = 5 |
|||
| Porter et al. (2015) | UPENN | 14 | Refractory CLL | 0.08–1.4 × 108 cells/m2 | scFv-4-1BB-CD3ζ (2nd generation) (anti-CD 19) |
Autologous | Fludarabine/cyclophosphamide 3, pentostatin/cyclophosphamide 5, bendamustine 6 | 4 | 4 CLL = 4 |
6 | |
| Cruz et al. (2013) | BCM | 8 | Relapsed B-ALL, 1 Pre-BALL2 B-ALL1 B-CLL4 |
1.5–4.5 × 107 cells/m2, and 1.2 × 108 cells/m2 | scFv-CD28-CD3ζ (2nd generation) or scFv-CD3ζ (1st generation) (Anti-CD19) |
Allogenic | NA | 3 Pre-B ALL = 2 Pre-ALL = 1 |
1 CLL | 1 CLL | 3 CLL = 2 Pre-B-ALL = 1 |
| Savoldo et al. (2011) | BCM | 6 | Relapsed or refractoryNHL 1SLL 2 Follicular 3 DLBCL |
1–2 × 108 cells/m2 | scFv-CD28-CD3ζ (2nd generation) or scFv-CD3ζ (1st generation) (anti-CD19) |
Autologous | NA | 4 Lym = 4 |
2 Lym = 2 |
||
| Jensen et al. (2010) | COH | 4 | Relapsed diffuse large cell lymphoma (DLCL)2 Relapsed follicular lymphoma (FL)2 |
1 × 108 – 2 × 109 cells/m2 | scFv-CD3ζ (1st generation) (anti-CD 19 and anti-CD 20) | Autologous | HSCT/ Fludarabine Rituximab3 |
2 Lym | 2 Lym | ||
| Wang et al. (2014) | Chinese PLA General Hospital |
7 | Relapsed or refractory CD20 + DLBCL | NR | scFv-CD-137- CD3ζ (2nd generation) (Anti-CD 20) |
Autologous | Cyclophosphamide, Vincristine, Doxorubicin, Etoposide and Carboplatin cytarabine. | 1 Lym = 1 |
3 Lym | 1 Lym | 1 Lym |
| Dai et al. (2015) | Chinese PLA General hospital | 9 | Relapsed and refractory ALL | 1 × 106 – 1.27 × 107 cells/kg | scFv-CD-137- CD3ζ (2nd generation) (anti-CD 19) |
Autologous/a llogenic (n = 2) | C-MOAD2, none7 | 2 ALL | 2 ALL | 3 ALL | |
| Till et al. (2012) | Fred hutchins on cancer research center, seattle, WA | 4 | MCL 3 FL 1 |
1 × 108 – 3.3 × 109 cells/m2 |
scFv-CD-137-CD- 28-CD3ζ (3rd generation) (Anti-CD20) |
Autologous | Rituximab3, fenretinide2, CHOP4, fludarabine1, bortezomib | 1 Lym = 1 |
2 Lym = 2 |
||
| Till et al. (2008) | Fred Hutchins on Cancer Research Center, Seattle, WA | 7 | FL 7 | 108/m2 – 3.3 × 109 cells/m2 | CD3ζ (1st generation) (anti-CD20) |
Autologous | Cyclophosphamide, vincristine, and prednisone (CVP) 4 FND = fldarabine, mitoxantrone and dexamethasone2 None2 131I-tositumomab 1 |
2 Lym | 1 Lym | 4 Lym | |
| Turtle (2015) | Fred Hutchins on Cancer Research Center, Seattle, WA | 34 | CLL 6 DLBCL18 FL6 MCL4 |
2 × 105 – 2 × 107 cells/kg | scFv, CD-137, CD3ζ (anti-CD19) | Autologous | Cyclophosphamide +/- etoposide or cyclophosphamide andfludarabine. |
9 CLL = 3 Lym = 6 |
9 CLL = 1 Lym = 8 |
11 CLL = 2 Lym = 9 |
|
| Park (2015) | MSKCC | 45 | Relapse/refractory ALL |
1 × 106 to 3 × 106 cells/kg | scFv-CD28-CD3ζ (2nd generation) (anti-CD 19) |
Autologous | Cyclophosphamide or cyclophosphamide+ fludarabine. | 37 | |||
ALL: Acute lymphoblastic leukemia; BCM: Baylor College of Medicine; CLL: Chronic lymphocytic leukemia; COH: City of hope; HSCT: Hematopoietic stem cell transplantation; MSKCC: Memorial Sloan-Kettering Cancer Center; NCI: National Cancer Institute; scFv: Single-chain variable fragment.