Table 2.
List of clinical trials of UCAR-T therapy with available results. Updated till 07/04/2024.
| Title | Safety assessment population (N) | CRSN (%) | ICANSN (%) | InfectionsN (%) | GVHDN (%) | Efficacy assessment population (N) | ORRN (%) | CRN (%) | Sponsor | Strategies | Target | Indication | Phase of study | Location |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| UCAR-T | ||||||||||||||
| ALLO-501[30] | 46 | Gr I–II: 10 (21.7); ≥Gr III: 1 (2.2) | ≥Gr II: absent | ≥Gr III: 11 (23.9) | absent | 32 | 24(75) | 16(50) | Allogene Therapeutics | Disruption of TRAC and CD52 genes by TALENs | CD19 | relapsed/refractory (r/r) B-Lymphoma | Phase 1 | US |
| TRUUCAR™ GC502[31] | 4 | Gr I–II: 1(33.3); ≥Gr III: 2(66.7) | ≥Gr II: absent | absent | absent | 4 | 4(100) | 3(75) | Gracell Biotechnologies | TRAC and CD7 loci were disrupted | CD19/CD7 | relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) | Phase 1 | China |
| ALLO-715[32] | 52 | Total: 27(52);≥Gr III: 1 (1.9) | Gr I–II: 5(1)] | Total: 29(56); ≥Gr III:(29) | absent | 36 | 27(75) | 18(50) | Allogene Therapeutics | Lymphodepletion with an anti-CD52 antibody (ALLO-647)-containing regimen | BCMA | r/r multiple myeloma | Phase 1 | US |
| UCART22[33] | 3 | Gr I–II: 2(67) | absent | – | – | 3 | 2 (66.7) | 1 (33.3) | Cellectis | Disruption of TRAC and CD52 genes by TALENs | CD22 | B-ALL | Phase 1 process 2 | US |
| CYAD-211[34] | 9 | Gr I: 1(11) | absent | Gr I–II: 2(22) | absent | 9 | 2 (12.6) | – | Celyad Oncology | Use of shRNA to silence mRNA coding for the CD3ζ component of the TCR | BCMA | r/r Multiple Myeloma | Phase 1 | US |
| CTX110[35] | 32 | Total: 18 (56.3); ≥Gr III: absent | Total: 3 (9.4); ≥Gr III: 2 (6.2) | ≥Gr III: 4 (12.5) | absent | 32 | 18 (56.3) | 11 (34.4) | CRISPR Therapeutics | Disruption of TRAC gene by CRISPR/Cas9 | CD19 | B cell malignancies | Phase 1 | US |
| FT819[36] | 12 | ≤Gr II: 3(25) | absent | – | absent | – | – | – | Fate Therapeutics | iPSc derived T cells, disruption of TRAC gene by CRISPR/Cas9 | CD19 | B cell malignancies | Phase 1 | US |
| ThisCART19A [37] | 8 | Gr2: 6(75) ≥Gr III: 2(25) | Total: 3 (37.5) | Total: 1 (12.5) | absent | 7 | – | 7(100) | Fundamenta Therapeutics | Intracellular retention of TCR/HLA-I | CD19 | r/r B-ALL and relapsed non-Hodgkin Lymphoma (NHL) | Phase 1 | China |
| UCART19[38] | 21 | 19(91); ≥Gr III: 3(14) | Gr I–II: 8(38); ≥Gr III: absent | 13(62) | Gr I: 2(10); ≥Gr II: absent | 21 | – | 14(67) | Servier | Disruption of TRAC and CD52 genes by TALENs technology | CD19 | r/r B-ALL | Phase 1 | US |
| P-BCMA-ALLO1[39] | 24 | Gr I: 3(14) | Gr I: 1(4) | – | absent | – | – | – | Poseida Therapeutics | Disruption of TRBC and B2 M genes by the Cas-CLOVER™ Gene Editing tool | BCMA | Multiple Myeloma | Phase 1 | US |
| PBCAR0191[40] | 15 | Total: 9(60); ≥Gr III: absent | Total: 4 (26.6); ≥Gr III: 1 (6.6) | Total: 6(40) | absent | 15 | – | 9(60) | Precision BioSciences | Disruption of TRAC gene by the versatile genome-editing platform ARCUS | CD19 | B-ALL | Phase 1 - 2 | US |
| TT52CAR19[41] | 6 | Gr II: 2 (33.3) | Gr IV: 1 (16.6) | – | Gr I: 1 (16.6) | 6 | – | – | University College, London | Disruption of TRAC and CD52 genes by CRISPR/Cas9 | CD19 | B-ALL | Phase 1 | UK |
| WU-CART-007[42] | 18 | Gr I–II: 13(72) Gr III: 1(5.56) | Gr I: 1 (5.56) | Total: 2 (11.1) | absent | 12 | – | 7 (58.3) | Washington University School of Medicine | Disruption of CD7 & TRAC genes by CRISPR/Cas9 | CD7 | r/r T-Cell Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma (T-ALL/LBL) | Phase 1 | US |
| P. MUC1C-ALLO1[43] | 7 | absent | absent | – | absent | – | – | – | Poseida Therapeutics | Disruption of TRBC and B2 M genes by the Cas-CLOVER™ Gene Editing tool; iCasp9-based safety switch gene | Mucin1 cell surface associated C-Terminal (MUC1-C) antigen | Advanced or Metastatic Solid Tumors | Phase 1 | US |
| CTA101[44] | 6 | Total: 6(100), Gr I:3(50), GrII:2 (33.3), GrIII:1 (16.6) | absent | Total: 6(100), GrI:1 (16.6), GrII:2 (33.3), GrIII:3(50) | absent | 6 | 6(100) | 2 (33.3) | Zhejiang University | TRAC and CD52 knockout by Cas9 | CD19/CD22 | r/r B-ALL | Phase 1 | China |
| RD13–01[45] | 12 | Gr I-II: 10 (83.3), ≥Gr III: absent | absent | 12(100) | absent | 11 | 9 (88.8) | 7 (63.6) | Zhejiang University | CD7, TCR/CD3 knockout by CRISPR/Cas9 | CD7 | r/r T-ALL/LBL | Phase 1 | China |
| CARCIK-CD19[46] | 13 | GrI–II: 3(23), ≥Gr III: absent | absent | 4(30) | absent | 13 | – | 8 (61.5) | Fondazione Matilde Tettamanti Menotti De Marchi Onlus | Sleeping beauty transposon induction of CIK cells | CD19 | r/r B-ALL | Phase 1 | Italy |
| SC291[47] | 1 | absent | absent | – | – | – | – | – | MD Anderson Cancer Center | CD3 and HLA class I/II gene knoout&CD47 overexpression | CD19 | NHL and Chronic Lymphocytic Leukemia (CLL) | Phase 1 | US |
| AVC-101 (UniCAR-T-CD123)[48] | 19 | Gr I-II: 12(63.2); Gr III: 3(15.8) | Gr II: 1 (5.3) | – | – | 15 | 8(53) | – | – | Adapter CAR-T consists of a universal CAR-T cell (UniCAR-T) and a CD123 targeting module ™ | CD123 | r/r AML | Phase 1 | Germany |
| CD33CART [49] | 19 | Total: 13(68); ≥Gr III: 4(21) | Total: 1(5) | – | – | 19 | – | 2(11) | Center for International Blood and Marrow Transplant Research | – | CD33 | r/r AML | Phase 1 | US |
| Nathali-01[50] | 3 | 3(100) | absent | – | absent | 3 | 3(100) | 2 (66.7) | Cellectis | Inactivation of TRAC and CD52 by TALENs | CD20, CD22 | r/r NHL | Phase 1 | US |
| BE-CAR7[51] | 3 | 3(100) | 2 (66.7) | 1 (33.3) | 1 (33.3) | – | – | – | Great Ormond Street Hospital for Children NHS Foundation Trust | CRISPR/nCas9 base editing to inactivate three genes encoding CD52 and CD7 receptors and the β chain of the αβ T-cell receptor | CD7 | relapsed T-ALL | Phase 1 | UK |