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. 2022 Oct 19;21:201. doi: 10.1186/s12943-022-01669-8

Table 2.

Multispecific CAR-T cell therapy in hematological tumors

Condition Clinical trials (phase and number) Targeting
domain		 Age Enrollment Start Date Locations Singaling domains Response Dose (cells/kg or cells/m2) Toxicity Reference
B-NHL Phase 1 (NCT03233854) CD19/CD22 Adult, Older Adult 21 1-Sep-17 Stanford University, School of Medicine; Palo Alto, California, United States 4-1BB-CD3ζ 6CR 3 ×  106 CRS gr. 3–4 (5%), Neurotoxicity gr.3–4 (0%) [47]
Phase 2 (NCT03196830) CD19/CD22 Child, Adult, Older Adult 32 1-Jun-17

the First Affiliated Hospital of Soochow University the First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

 4-1BB-CD3ζ 11CR a total dose of 3.690×  108–3.285×  109 CRS gr. 3–4 (28%), Neurotoxicity gr.3–4 (12.5%) [48]
Phase 1 (ChiCTR1800015575) CD19/CD22 Child, Adult, Older Adult 16 10-Apr-18 the First Affiliated Hospital, School of Medicine, Zhejiang University 4-1BB-CD3ζ 10CR 1–10× 106 CRS gr. 3–4 (6%), Neurotoxicity gr.3–4 (0%) [49]
Phase 1/2 (NCT03097770) CD19/CD20 Child, Adult, Older Adult 87 1-Apr-17 Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital Beijing, Beijing, China 4-1BB-CD3ζ 61CR 0.5× 106–8× 106 CRS gr. 3–4 (10%), Neurotoxicity gr.3–4 (2%) [50]
Phase 1 (NCT03019055) CD19/CD20 Adult, Older Adult 19 16-Oct-17 Froedtert Hospital & Medical College of Wisconsin, Milwaukee, Wisconsin, United States 4-1BB-CD3ζ 12CR 2.5 ×  105–2.5× 106 unknown [51]
CD19/CD70,CD19/20/22,CD19/CD37 [421–423]
B-ALL Phase 1 (ChiCTR1800015575) CD19/CD22 Child, Adult, Older Adult 15 10-Apr-18 the First Affiliated Hospital, School of Medicine, Zhejiang University 4-1BB-CD3ζ 13CR 1.04× 106–7.02× 106 CRS gr. 3–4 (13%), Neurotoxicity gr.3–4 (0%) [89]
Phase 1 (NCT03233854) CD19/CD22 Adult, Older Adult 17 1-Sep-17 Stanford University, School of Medicine, Palo Alto, California, United States 4-1BB-CD3ζ 15CR 3× 106 CRS gr. 3–4 (6%), Neurotoxicity gr.3–4 (18%) [47]
Phase 1 (NCT03185494) CD19/CD22 Child, Adult, Older Adult 6 1-Aug-17 Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital Beijing, Beijing, China 4-1BB-CD3ζ 6CR 1.7× 106–3×  106 CRS gr. 3–4 (0%), Neurotoxicity gr.3–4 (0%) [87]
Phase 1 (NCT03289455) CD19/CD22 Child, Adult 15 26-Jun-17

Great Ormond Street Hospital for Children NHS Foundation Trust London, United Kingdom; University College London Hospitals NHS Foundation Trust

London, United Kingdom; Royal Manchester Children’s Hospital

Manchester, United Kingdom

 4-1BB-CD3ζ 13CR 0.3–2× 106,3 × 106,4.3–5×  106 CRS gr. 3–4(0%), Neurotoxicity gr.3–4 (7%) [424]
Phase 1 (ChiCTR-ONC-17013648) CD19/CD22 Child, Adult 21 4-Dec-17 Beijing Boren Hospital, Beijing, China 4-1BB-CD3ζ 14CR 0.486–5.0× 105 (CD19), 0.32–5.0× 105 (CD22) CRS gr. 3–4 (0%), Neurotoxicity gr.3–4 (0%) [86]
CD20/CD22,CD19/CD123,CD19/BAFF-R [82, 425, 426]
T-ALL CD5/CD7 [66]
AML CD123/CD19,FLT3/NKG2DL,CD123/CLL1,CD13/TIM3,CD123/FRβ [427–431]
CLL Phase 1 (NCT03019055) CD19/CD20 Adult, Older Adult 3 16-Oct-17 Froedtert Hospital & Medical College of Wisconsin, Milwaukee, Wisconsin, United States 4-1BB-CD3ζ 2CR 2.5 × 105–2.5×  106 unknown [51]
MM Phase 1 (ChiCTR1800018143) BCMA/CD38 Adult, Older Adult 23 1-Sep-18 Institute of Hematology, Union Hospital Affiliated to Tongji Medical College, Huazhong University of science and technology 4-1BB-CD3ζ 12CR 0.5,1.0,2.0,3.0 and 4.0× 106 CRS gr. 3–4 (22%), Neurotoxicity gr.3–4 (0%) [169]
Phase 2 (ChiCTR1800017051) BCMA/CD38 Adult, Older Adult 22 1-Jun-18 The first central hospital of Tianjin, Tianjin, China 4-1BB-CD3ζ 12CR 2× 106 (BCMA), 2×  106 (CD38) CRS gr. 3–4 (27%), Neurotoxicity gr.3–4 (0%) [170]
Phase 2 (ChiCTR-OIC-17011272) BCMA/CD19 Adult, Older Adult 62 1-May-17 The Affiliated Hospital of Xuzhou Medical University, Jiangsu, China 4-1BB-CD3ζ 37CR 1× 106 (BCMA), 1×  106 (CD19) CRS gr. 3–4 (10%), Neurotoxicity gr.3–4 (3%) [171]