Table 1.
CAR T-cell strategies for hematological cancer
| Target | CAR format | Co-stim domain | Nr. of evaluated patients | CR (%) | CRS grade ≥ 3 (%) | Neurotox. grade ≥ 3 (%) | Clinical trial identifier | References |
|---|---|---|---|---|---|---|---|---|
| Acute lymphoblastic leukemia | ||||||||
| CD19# | Single | 4-1BB | 63 | 63 | 49 | 18 | NCT02435849 | [7] |
| CD22 | Single | 4-1BB | 21 | 57 | 0 | N/A | NCT02315612 | [8] |
| CD19/CD22 | Tandem | 4-1BB | 6 | 100 | 0 | 0 | NCT03185494 | [10] |
| CD19/CD22 | Dual | OX40/4-1BB | 7* | 100 | 0 | 0 | NCT03289455 | [11] |
| CD19/CD123 | Dual | 4-1BB/4-1BB | – | – | – | – | – | [12] |
| CD19/CD123 | Pooled | CD28 + CD27 | 3 | 100 | 0 | 0 | NCT03125577 | [13, 14] |
| CSPG4 | Single | CD28 | – | – | – | – | – | [15] |
| BAFF-R | Single | 4-1BB | – | – | – | – | NCT04690595 | [16, 17] |
| Chronic lymphocytic leukemia | ||||||||
| CD19 | Single | 4-1BB | 3 | 66 | – | – | NCT01029366 | [18, 19] |
| CD19 + ibrutinib | Single | 4-1BB | 19 | 83 | 0 | 26 | NCT01865617 | [20] |
| CD19/CD20 | Tandem | 4-1BB | 22*** | 64 | 5 | 14 | NCT03019055 | [21] |
| κ light chain | Single | CD28 | 16**** | 12.5 | 0 | – | NCT00881920 | [22] |
| FcμR | Single | CD28 | – | – | – | – | – | [23] |
| Multiple myeloma | ||||||||
| BCMA# | Single | 4-1BB | 128 | 32.8 | 5 | 3 | NCT03361748 | [24] |
| BCMA***** | Tandem | 4-1BB | 17 | 76.4 | 53.8 | – | NCT03090659 | [25] |
| BCMA/TACI | Single***** | CD28 + OX40 | 11 | 0 | 0 | 0 | NCT03287804 | [26, 27] |
| CD19 + ASCT | Single | 4-1BB | 11 | 1 | 0 | 0 | NCT02135406 | [28, 29] |
| CD38 | Single | 4-1BB | – | – | – | – | – | [30, 31] |
| CD138 | Single | 4-1BB | 5 | 0 | – | – | NCT01886976 | [32] |
| CS1****** | Single | CD28 | – | – | – | – | NCT03958656 | [33] |
| GPRC5D | Single | 4-1BB | – | – | – | – | NCT04555551 | [34] |
| Integrin β7 | Single | CD28 | – | – | – | – | – | [35] |
| NKG2D ligands | Single******* | None | 12 | 0 | 0 | – | NCT02203825 | [36] |
| CS1/BCMA | Tandem | 4-1BB | – | – | – | – | – | [37] |
| CD19/BCMA | Pooled | 4-1BB/4-1BB | 21 | 57 | 5 | – | ChiCTR-OIC-17011272 | [38] |
| B-cell lymphoma | ||||||||
| CD19# | Single | CD28 | 68 | 59 | 15 | 31 | NCT02601313 | [39] |
| CD30 | Single | 4-1BB | 18 | 0 | 0 | 0 | NCT022595 | [40] |
| CD37 | Single | 4-1BB | – | – | – | – | NCT04136275 | [41] |
| CD79b | Single | CD28-4-1BB | – | – | – | – | ChiCTR-OPN-16008526 | [42] |
| CD79b/CD19 | Tandem | 4-1BB | – | – | – | – | – | [43] |
| T-cell lymphoma | ||||||||
| TRBC1 | Single | CD28 + OX40 | – | – | – | – | NCT03590574 | [44] |
| CD30 | Single | CD28 | 1 | 100 | 0 | 0 | NCT02690545 | [45] |
| CD37 | Single | 4-1BB | – | – | – | – | NCT04136275 | [41] |
#Approved product; –No data available; N/A not available; *10 patients treated but only 7 evaluable at cut-off-date; **3 patients with CLL, remaining patients diagnosed with other r/r B-cell malignancies; ***2 patients with CLL, remaining patients diagnosed with other r/r B-cell malignancies; ****Biepitopic; *****Utilizes full length APRIL domain as binder; ******Suicide switch; *******Utilizes full length extracellular NKG2D domain as binder. CSPG4 Chondroitin Sulfate Proteoglycan-4, BAFF-R B-cell activating factor receptor, BCMA B-cell maturation antigen; TACI Transmembrane activator and CAML interactor; GPRC5D G protein-coupled receptor class C group 5 member-DTRBC1 T cell receptor beta constant-1