Table 1 The preliminary results of dual and combined CAR-T cell therapy for B cell malignancies
Researchers | Condition | Target | Design | Co-stimulation domain | Enrolled pts | Primary outcome | Long-term follow-up |
|---|---|---|---|---|---|---|---|
Hossain et al. [21] | B cell malignancies | CD 19 and CD 22 | One CAR with two binding sites | 4-1BB | 5 DLBCL pts, 2 ALL pts | 2/6 pts achieved CR; 3/6 pts achieved PR; 1/6 pts had PD | Two pts remained CR at two and 3 months, 2 pts remained PR and the other one died of PD. |
Shah et al. [22] | B-NHL | CD 19 and CD 20 | One CAR with two binding sites | 4-1BB | 3 MCL pts, 2 DLBCL pts, and 1 CLL pts | 2/6 pts achieved C R; 2/6 pts achived PR, and 2/6 pts had PD | 2 pts remained in CR at 3 and 9 months |
Amrolia et al. [23] | B-ALL | CD 19 and CD 22 | One vector encoding two CARs | 4-1BB for CD 19, OX4O for CD 22 | 9 CAR pediatric pts | All 9 pts achieved MRD-CR | 3 pts relapsed within 1 year after treatment. |
Ardeshna et al. [24] | D LBCL | 11 adult pts | The lowest dose: 2/7 pts achieved CR, 2/7 pts achived PR The higher dose: 2/4 pts achieved CR | NA | |||
Schult et al. [25] | B-ALL | CD 19 and CD 22 | One CAR with two binding sites | 4-1BB | 10 pediatric pts and 9 adult pts | 11/12 pts achieved CR, 1/12 pts had PD | The OSs was 92% with a median follow-up of 9.5 months |
Dai et al. [26] | B-ALL | CD 19 and CD 22 | One CAR with two binding sites | 4-1BB | 6 adult pts | All 6 pts achieved CR | 3 relapse at 3 monthd, 5 months, and 10 months after treatment |
Yang et al. [27] | B-ALL | CD 19 and CD 22 | Two vectors encoding two CAR | 4-1bb and extra PD-L1 for CD 22 | 5 children and 10 adults | All 15 pts achieved CR, 14 of them achieved MRD | 11 pts bridged allo-HSCT remained in remission state with a median follow-up of 133 days. 2 pts without allo-HSCT relapsed on day 240 and day 105 after treatment |
Yang et al. [28] | B-ALL | CD 19 and CD 22 | One CAR with two binding sites | 4-1BB | 4 adults and 13 pediatrics pts | The low dose: 3/4 pts had non-response and 1/4 achieved MRD + CR.The medium dose: all 7 pts achieved CR, 6/7 pts had MRD-CR | No one relapsed with a median follow-up time of 60 days |
Gardner et al. [29] | B-ALL | CD 19 and CD 22 | Two vectors encoding two CARS | 4-1BB | 7 young adult or pediatric pts | 5/7 pts achieved CR, 4/7 of them achieved MRD– | NA |
Wang et al. [30] | B-ALL | CD 19 and CD 22 | Manufacture and infuse separately | CD 28 and 4-1BB for both CAR | 51 adult pts | 48/50 pts achieved MRD-CR, 2/50 pts achieved PR | The median PFS was 13.6 months,The median O S was 31.0 months |
| Â | B-NHL | 38 adult pts | 18/36 pts achieved CR, 8/36 pts achieved PR | The median PFS was 9.9 months ,The median O S was 18.0 months |