Table 2 Preclinical data of CLL-1 CAR-T cell therapy
Study | Generation | Costimulatory domain | Transduction method | In vitro efficacy | Impact on normal cells | NSG mice model |
|---|---|---|---|---|---|---|
Tashiro 2017 [31] | Second | 4-1BB | Retrovirus | Potent and specific cytotoxicity against CLL-1+ targets | Cytotoxic to mature myeloid cells, sparing myeloid progenitor cells | Significantly prolonged survival |
Laborda 2017 [50] | Second | 4-1BB | Lentivirus | Robust toxicity on AML cell lines and patient-derived AML blast | Minor decrease in CFU-GM, no impact on BFU-E, CFU-GEMM, and HSC; Neutropenia. | Complete elimination of leukemia by day 90 |
Kenderian 2016 [51] | Second | 4-1BB | Lentivirus | Modest effect to primary AML blasts; highly effective to CLL-1+ AML cell lines. | N/A | 100% survival at day 200 in combination with cytarabine while 20% in untreated. |
Wang 2018 [28] | Third | CD28 and 4-1BB | Lentivirus | Specific and strong lysis of AML cell line and primary AML blasts | Eradicating mature granulocytes, variable elimination of progenitors, sparing HSC | Significantly decreased leukemia burden and prolonged survival |
Togni 2018 [52] | Second | 4-1BB | Lentivirus | Dose-dependent killing efficacy | N/A | Significantly prolonged survival with CLL-1 CART-A while not with CART-B |