Table 2.
Current clinical trials of CAR T cell-based anti-tumor therapy using “next-generation” CAR strategies.
| CAR strategy | Target antigen | Cancer type | Phase | Status | NCT No. |
|---|---|---|---|---|---|
| NB-CAR | CD7 | Hematologic malignancies | I | Unknown | NCT04004637 |
| NB-CAR+ tandem CAR | CD19/CD20 | B cell malignancies | I | Unknown | NCT03881761 |
| BCMA | MM | I/II | Unknown | NCT03090659 | |
| NRB-CAR | CD70 | Various*1 | I/II | Suspended | NCT02830724 |
| Fc | Various*2 | NA | Terminated | NCT02840110 | |
| Fc (HER2) | Solid tumors | I | Terminated | NCT03680560 | |
| Fc (CD20) | B cell malignancies | I | Completed | NCT02776813 | |
| Fc (CD20) | B cell malignancies | I | Terminated | NCT03189836 | |
| Fc (BCMA) | MM | I | Terminated | NCT03266692 | |
| NKG2D ligand | Various*3 | I | Not yet recruiting | NCT05302037 | |
| NKG2D ligand | Solid tumors | I | Unknown | NCT04107142 | |
| NKG2D ligand | Solid tumors | I | Recruiting | NCT05131763 | |
| NKG2D ligand | Hematologic malignancies | I | Completed | NCT03612739 | |
| NKG2D ligand | Hematologic malignancies | I | Withdrawn | NCT03018405 | |
| NKG2D ligand | Hematologic malignancies | I/II | Unknown | NCT05248048 | |
| NKG2D ligand | Colorectal cancer | Early I | Recruiting | NCT03310008 | |
| NKG2D ligand | Colorectal cancer | I | Unknown | NCT03692429 | |
| NKG2D ligand | Colorectal cancer | I | Recruiting | NCT04991948 | |
| NKG2D ligand | Colorectal cancer | I | Recruiting | NCT03370198 | |
| NKG2D ligand | Colorectal cancer | I | Unknown | NCT03466320 | |
| NKG2D ligand | AML | I/II | Completed | NCT04167696 | |
| NKG2D ligand | AML | I | Recruiting | NCT05131763 | |
| PSMA | Prostate cancer | I | Recruiting | NCT04768608 | |
| NRB-CAR + OFF-switch | PD-L1 | GBM | I | Unknown | NCT02937844 |
| NLB-CAR | BCMA/TACI | MM | I/II | Terminated | NCT03287804 |
| BCMA/TACI | MM | I | Recruiting | NCT05020444 | |
| BCMA/TACI | MM | Early I | Not yet recruiting | NCT04657861 | |
| ErbB family | HNSCC | I | Recruiting | NCT01818323 | |
| GMR | Hematologic malignancies | I/II | Recruiting | jRCT2033210029 | |
| ICAM-I | Thyroid cancer | I | Recruiting | NCT04420754 | |
| IL-13Rα2 | GBM | I | Active, not recruiting | NCT02208362 | |
| IL-13Rα2 | GBM | I | Recruiting | NCT04003649 | |
| IL-13Rα2 | GBM | I | Recruiting | NCT04510051 | |
| IL-13Rα2 | GBM | I | Recruiting | NCT04661384 | |
| MMP-2 | GBM | I | Recruiting | NCT04214392 | |
| CARVac | CLDN6 | Solid tumors | I/II | Recruiting | NCT04503278 |
| Dual-targeting CAR | BCMA/CS1 | MM | Early I | Unknown | NCT04156269 |
| BCMA/GPRC5D | MM | I | Not yet recruiting | NCT05325801 | |
| CD123/CD33 | Hematologic malignancies | Early I | Unknown | NCT04156256 | |
| CD123/CLL1 | AML | II/III | Unknown | NCT03631576 | |
| CD19/BCMA | MM | I | Recruiting | NCT05412329 | |
| CD19/BCMA | MM | I | Recruiting | NCT04162353 | |
| CD19/BCMA | MM | I/II | Recruiting | NCT03455972 | |
| CD19/BCMA | MM | I | Unknown | NCT03767725 | |
| CD19/BCMA | MM | Early I | Recruiting | NCT04236011 | |
| CD19/BCMA | MM | I/II | Recruiting | NCT04714827 | |
| CD19/BCMA | MM | I | Unknown | NCT04194931 | |
| CD19/BCMA | MM | Early I | Unknown | NCT04182581 | |
| CD19/BCMA | MM | Early I | Unknown | NCT04412889 | |
| CD19/BCMA | MM | I | Unknown | NCT03706547 | |
| Dual-targeting CAR | CD19/BCMA | MM | Early I | Not yet recruiting | NCT04617704 |
| CD19/CD20 | NHL | I | Recruiting | NCT05421663 | |
| CD19/CD20 | NHL | I/II | Unknown | NCT04553393 | |
| CD19/CD20 | NHL | I | Unknown | NCT04693676 | |
| CD19/CD20 | NHL | I | Unknown | NCT04655677 | |
| CD19/CD20 | NHL | I | Unknown | NCT04696432 | |
| CD19/CD20 | NHL | I/II | Recruiting | NCT04697940 | |
| CD19/CD20 | NHL | Early I | Suspended | NCT04697290 | |
| CD19/CD20 | ALL | I | Recruiting | NCT04049383 | |
| CD19/CD20 | B cell malignancies | I | Completed | NCT03019055 | |
| CD19/CD20 | B cell malignancies | I | Completed | NCT04260932 | |
| CD19/CD20 | B cell malignancies | I | Completed | NCT04260945 | |
| CD19/CD20 | B cell malignancies | I/II | Recruiting | NCT04186520 | |
| CD19/CD20 | B cell malignancies | I/II | Completed | NCT03097770 | |
| CD19/CD20 | B cell malignancies | Early I | Unknown | NCT04156178 | |
| CD19/CD20 | B cell malignancies | I | Terminated | NCT04160195 | |
| CD19/CD20 | B cell malignancies | I/II | Unknown | NCT03207178 | |
| CD19/CD20 | DLBCL | I | Recruiting | NCT04215016 | |
| CD19/CD20 | DLBCL | I | Unknown | NCT04486872 | |
| CD19/CD20 | DLBCL | I/II | Unknown | NCT02737085 | |
| CD19/CD20 | Hematologic malignancies | I | Unknown | NCT03271515 | |
| CD19/CD20 | Hematologic malignancies | Early I | Unknown | NCT04700319 | |
| CD19/CD20/CD22 | Hematologic malignancies | I/II | Unknown | NCT03398967 | |
| CD19/CD20/CD22 | Hematologic malignancies | I | Recruiting | NCT05418088 | |
| CD19/CD20/CD22 | B cell malignancies | I | Recruiting | NCT05318963 | |
| CD19/CD20/CD22 | B cell malignancies | I | Recruiting | NCT05094206 | |
| CD19/CD20/CD22 | B cell malignancies | I | Recruiting | NCT05388695 | |
| CD19/CD22 | B cell malignancies | I | Recruiting | NCT04204161 | |
| CD19/CD22 | B cell malignancies | Early I | Unknown | NCT03825731 | |
| CD19/CD22 | B cell malignancies | I | Unknown | NCT03463928 | |
| CD19/CD22 | B cell malignancies | I | Recruiting | NCT04007029 | |
| CD19/CD22 | B cell malignancies | I | Withdrawn | NCT04094766 | |
| CD19/CD22 | B cell malignancies | I | Recruiting | NCT03233854 | |
| CD19/CD22 | B cell malignancies | I/II | Recruiting | NCT04715217 | |
| CD19/CD22 | B cell malignancies | I/II | Recruiting | NCT04782193 | |
| CD19/CD22 | B cell malignancies | I | Terminated | NCT03593109 | |
| CD19/CD22 | B cell malignancies | I/II | Suspended | NCT03098355 | |
| CD19/CD22 | B cell malignancies | I/II | Recruiting | NCT04788472 | |
| CD19/CD22 | B cell malignancies | I | Recruiting | NCT03448393 | |
| CD19/CD22 | DLBCL | I/II | Active, not recruiting | NCT03287817 | |
| CD19/CD22 | HNL | II | Recruiting | NCT04539444 | |
| CD19/CD22 | NHL | Early I | Recruiting | NCT04303247 | |
| CD19/CD22 | NHL | I/II | Not yet recruiting | NCT04626908 | |
| CD19/CD22 | Hematologic malignancies | I | Recruiting | NCT03330691 | |
| CD19/CD22 | Hematologic malignancies | I/II | Not yet recruiting | NCT04029038 | |
| CD19/CD22 | Hematologic malignancies | I | Active, not recruiting | NCT02443831 | |
| CD19/CD22 | Hematologic malignancies | I/II | Unknown | NCT03185494 | |
| CD19/CD22 | ALL | I/II | Recruiting | NCT04714593 | |
| CD19/CD22 | ALL | I/II | Recruiting | NCT04499573 | |
| CD19/CD22 | ALL | I | Recruiting | NCT03919526 | |
| CD19/CD22 | ALL | I/II | Recruiting | NCT04781634 | |
| CD19/CD22 | ALL | I/II | Completed | NCT03289455 | |
| CD19/CD22 | ALL | I | Unknown | NCT04303520 | |
| CD19/CD22 | ALL | I | Not yet recruiting | NCT05223686 | |
| CD19/CD22 | ALL | I | Withdrawn | NCT05168748 | |
| CD19/CD22 | ALL | I/II | Recruiting | NCT04740203 | |
| Dual-targeting CAR | CD19/CD22 | ALL | Early I | Recruiting | NCT04626765 |
| CD19/CD22 | ALL | I | Unknown | ChiCTR-OIB-17013670 | |
| CD19/CD22 | ALL | I | Unknown | ChiCTR1800015575 | |
| CD19/CD22 | ALL | I | Active | EUDRA CT 2016–004680-39 | |
| CD19/CD22 | ALL | Early I | Active, not recruiting | NCT04034446 | |
| CD19/CD22 | ALL | I/II | Recruiting | NCT03614858 | |
| CD19/PD-L1 | Hematologic malignancies | I | Unknown | NCT03932955 | |
| CD19/PD-L1 | B cell malignancies | I | Recruiting | NCT04850560 | |
| CD20/CD22 | Hematologic malignancies | Early I | Recruiting | NCT04283006 | |
| CD33/CLL1 | Hematologic malignancies | Early I | Recruiting | NCT03795779 | |
| CD33/CLL1 | AML | Early I | Not yet recruiting | NCT05016063 | |
| CD33/CLL1 | AML | I | Recruiting | NCT05248685 | |
| CD38/BCMA | MM | I | Recruiting | ChiCTR1800018143 | |
| c-Met/PD-L1 | Hepatocellular Carcinoma | Early I | Unknown | NCT03672305 | |
| EGFR/B7H3 | Lung cancer / TNBC | Early I | Recruiting | NCT05341492 | |
| HER2/PD-L1 | Solid tumors | Early I | Recruiting | NCT04684459 | |
| CD33/CD123/CLL-1 | AML | I/II | Recruiting | NCT04010877 | |
| CD44v6/GD/Her2 | Breast cancer | I/II | Recruiting | NCT04430595 | |
| CD10/CD20/CD22 | ALL | Early I | Recruiting | NCT03407859 | |
| Multiple$1 | MM | I/II | Recruiting | NCT03196414 | |
| Multiple$2 | ALL | I/II | Recruiting | NCT04430530 | |
| Multiple$3 | AML | I/II | Unknown | NCT03222674 | |
| Multiple$4 | Lung cancer | I | Recruiting | NCT03198052 | |
| Multiple$5 | B cell malignancies | I/II | Recruiting | NCT04429438 | |
| Switchable CAR | CD19 | B cell malignancies | I | Recruiting | NCT04450069 |
| CRs-CAR | BCMA | MM | Early I | Not yet recruiting | NCT04727008 |
| CD19 | DLBCL | I | Recruiting | NCT04381741 | |
| CD19 | B cell malignancies | NA | Completed | NCT04833504 | |
| CD19 | B cell malignancies | II | Unknown | NCT03929107 | |
| CD30 | Hematologic malignancies | I | Recruiting | NCT03602157 | |
| EGFR | NSCLC | I | Recruiting | NCT04153799 | |
| EGFR | NSCLC | Early I | Recruiting | NCT05060796 | |
| PSMA# | Prostate cancer | I | Not yet recruiting | NCT04227275 | |
| PSMA# | Prostate cancer | I | Recruiting | NCT03089203 | |
| OFF-Switch CAR | BCMA | MM | I | Active, not recruiting | NCT03070327 |
| CD19 | MCL | II | Recruiting | NCT04484012 | |
| CD19 | Hematologic malignancies | I | Active, not recruiting | NCT03085173 | |
| CD22 | Hematologic malignancies | I | Active, not recruiting | NCT03244306 |
NB: nanobody; NRB: natural receptor-based; NL: natural ligand-based; AML: acute myeloid leukemia; MM: multiple myeloma; HNSCC: Head and neck squamous cell carcinoma; GBM: glioblastoma
*1
: Pancreatic cancer, renal cell carcinoma, breast cancer, melanoma, ovarian cancer
*2
: B cell lymphoma, multiple myeloma, solid tumors
*3
: Relapsed and refractory malignancies
MM: multiple myeloma; NHL: non-hodgkin’s lymphoma; DLBCL: diffuse large B-cell lymphoma; ALL: acute lymphocytic leukemia
CRs: chemokine/cytokine receptor; AML: acute myeloid leukemia; MM: multiple myeloma; DLBCL: diffuse large B-cell lymphoma; ALL: acute lymphocytic leukemia; TNBC: triple negative breast cancer; MCL: mantle cell lymphoma; NSCLC: non-small cell lung cancer
$1
: CD138, BCMA, CD19, and/or other antigens
$2
: CD22, CD123, CD38, CD10, and/or CD20
$3
: CD33, CD38, CD123, CD56, MUC1, and/or CLL1
$4
: GPC3, Mesothelin, Claudin18.2, GUCY2C, B7-H3, PSCA, PSMA, MUC1, TGFβ, HER-2, Lewis-Y, AXL, and/or EGFR
$5
: CD19, CD20, CD22, CD70, CD13, CD79b, GD2 and/or PSMA
#
: TGFβ-resistant by modifying CAR T cell with a dominant negative TGFβ receptor (TGFβRdn)