TABLE 1.
Selected clinical trials testing potential “off-the-shelf” CAR cell therapies.
| Cells | CAR | Diseases/Patients | 1°/2° outcomes | References | |
| No genome modification | |||||
| Allogeneic T cells | CD19-CAR | Relapsed or refractory CD19+ B cell malignancies | 1°: DLT, CR 2°: ORR, DOR, safety, tolerability, TRM | NCT04384393 | ThisCART19 |
| Allogeneic T cells | CD19-CAR | Elderly relapsed or refractory B-ALL | 1°: occurrence of adverse events 2°: overall response rate, DFS, OS | NCT02799550 | |
| Allogeneic T cells | alloCART-19 | Pediatric relapsed or refractory ALL | 1°: DLT 2°: AE, ORR, BOR | NCT04173988 | |
| Allogeneic T cells | NKG2D-based CAR-T plus inhibitory peptide T cell receptor (TCR) inhibiting molecule (TIM) to reduce signaling of the TCR complex through a non-gene edited approach | Metastatic colorectal cancer (mCRC) | 1°: DLT, ORR 2°: AE, safety, ORR, BOR, kinetics, clinical activity, PFS, EFS, OS | NCT03692429 | alloSHRINK trial |
| Genome modified | |||||
| Allogeneic T cells (TCRα/β disruption) | Anti-CS1 CAR (UCARTCS1A) | Relapsed or refractory MM | 1°: safety | NCT04142619 | MELANI-01 |
| Allogeneic T cells (TCRα/β disruption) | Anti-CD123 (UCART123) | Relapsed or refractory AML | 1°: safety, tolerability | NCT03190278 | AMELI-01 |
| Allogeneic T cells (TCRα/β disruption) | CD19-UCART | Relapsed or refractory B cell malignancies | 1°: DLT 2°: ORR, CART persistence | NCT03229876 | |
| Allogeneic T cells (TCRα/β disruption) | BCMA-UCART | Relapsed or refractory MM | 1°: ORR 2°: safety, tolerability, CART persistence | NCT03752541 | |
| Allogeneic T cells (TCRα/β disruption) | CD22-CAR (UCART22) | Relapsed or refractory CD22+ B-cell B-ALL | 1°: safety, tolerability | NCT04150497 | BALLI-01 |
| Allogeneic T cells (TCRα/β disruption) | CD19-UCART | Relapsed or refractory B-ALL | 1°: DLT 2°: safety, tolerability, objective remission rate and duration, PFS, OS | NCT02746952 | CALM |
| Allogeneic T cells (TCRα/β and B2M disruption) | UCART019 | Relapsed or refractory CD19+ leukemia and lymphoma | 1°: safety, feasibility, persistence 2°: tumor response, test for humoral immunity against murine CD19 scFv | NCT03166878 | |
| Allogeneic T cells (TCRα/β and B2M disruption) | CTX110 (CD19-CAR) | Relapsed or refractory B cell malignancies | 1°: DLT, ORR 2°: DOR, PFS, OS | NCT04035434 | |
| Allogeneic T cells (TCRα/β and B2M disruption) | CTX120 (BCMA-CAR) | Relapsed or refractory MM | 1°: AE, DLT, ORR 2°: PFS, OS | NCT04244656 | |
| Allogeneic T cells (TCRα/β and B2M disruption) | CTX130 (CD70-CAR) | Relapsed or refractory renal cell carcinoma | 1°: AE, DLT, ORR 2°: PFS, OS | NCT04438083 | |
| Allogeneic T cells (TCRα/β and B2M disruption) | Universal Dual CD19 + CD20-CAR or CD19 + CD22-CAR | Relapsed or refractory B-cell malignancies | 1°: safety, feasibility, persistence 2°: anti-tumor response, test for humoral immunity against murine CD19 scFv | NCT03398967 | |
| Donor T cells (CMV- or EBV-specific T cells derived from donor CD62L + TCM cells) | CD19-CAR | B cell malignancies after allogeneic transplant | 1°: safety, feasibility 2°: persistence, trafficking to bone marrow, function, CMV/EBV reactivation, elimination of CD19+ tumor cells | NCT01475058 | |
| Allogeneic EBV specific cytotoxic T-lymphocytes (EBV-CTLs) | CD19-CAR | B cell malignancies after allogeneic transplant or high risk for relapse | 1°: safety, persistence 2°: assess effects on leukemia progression, CAR-T cell survival and | NCT01430390 | |
| proliferation, long-term status of treated patients | |||||
| Allogeneic EBV specific T cells | Anti-CD30 CAR | Relapsed or refractory CD30+ lymphoma | 1°: DLT 2°: ORR, DOR, SD, PFS | NCT04288726 | |
| Other “off-the-shelf” CAR cells | |||||
| NK-92 cell line | CD33-CAR (CD28-CD137 (4-1BB)-CD3ζ) | Relapsed or refractory CD33+ AML | 1°: safety, feasibility 2°: anti-leukemia response, in vitro anti-AML cytotoxicity, test for development of humoral immunity against the murine anti-CD33 scFv | NCT02944162 | |
| NK-92 cell line | CD7-CAR (CD28-4-1BB-CD3ζ) | CD7 + leukemia and lymphoma | 1°: AE, toxicity profile 2°: clinical response, persistence | NCT02742727 | |
| NK-92 cell line | CD19-CAR | CD19+ leukemia and lymphoma | 1°: AE 2°: ORR | NCT02892695 | |
| Allogeneic NKT cells | CD19-CAR + IL-15 | Relapsed or refractory B cell malignancies | 1°: DLT 2°: persistence of modified cells, overall response | NCT03774654 | ANCHOR |
| Haploidentical/Allogeneic Gamma Delta (γδ) T cells | NKG2DL-targeting CAR | Relapsed or refractory solid tumors | 1°: DLT 2°: AE, efficacy, PFS, DOR | NCT04107142 | |
| Allogeneic Gamma Delta (γδ) T cells | CD19-CAR | High risk, relapsed CD19+ B cell malignancies | 1°: safety (adverse events) 2°: CAR γδ persistence, antitumor activity, MTD | NCT02656147 |
AE, adverse events; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; B-ALL, B-cell acute lymphoblastic leukemia; BOR, best overall response; CR, complete remission; DFS, disease-free survival; DLT, dose limiting toxicities; DOR, duration of response; EBV, Epstein Barr virus; MM, multiple myeloma; ORR, objective response rate; PFS, progression-free survival; OS, overall survival; scFv, single chain variable fragment; SD, stable disease; TRM, treatment related mortality.