Introduction
Safety strategy | Target | Identifier | Disease | Treatment arms | Phase | Stage | Sponsor | Comments |
---|---|---|---|---|---|---|---|---|
EGFRt + cetuximab | CD19 | NCT02028455 | CD19+ acute leukemia | Anti-CD19 CAR-T/EGFRt | I/II | Recruiting | Seattle Children’s Hospital | To study the MTD and efficacy of CAR-T cells |
NCT02146924 | High-risk ALL | Anti-CD19 CAR-T/EGFRt | I | Recruiting | City of Hope Medical Center | To study the side effects and best dose of CAR-T cells | ||
NCT01815749 | Recurrent or high-risk NHL | Anti-CD19 CAR-T/EGFRt +auto-HSCT | I | Active, not recruiting | City of Hope Medical Center | To study the side effects and best dose of CAR-T cells | ||
NCT03579888 | CD19+ lymphoid malignancies | Anti-CD19 CAR-T/EGFRt +Cyclophosphamide +Fludarabine | I | Not yet recruiting | M.D. Anderson Cancer Center | To study the side effects and best dose of CAR-T cells | ||
NCT02051257 | Recurrent B-cell NHL | Anti-CD19 CAR-T/EGFRt | I | Active, not recruiting | City of Hope Medical Center | To study the highest dose of memory enriched T cells | ||
NCT01865617 | R/R CLL, NHL or ALL | Anti-CD19 CAR-T/EGFRt | I/II | Recruiting | Fred Hutchinson Cancer Research Center | To study the side effects and best dose of CAR-T cells | ||
NCT03103971 | R/R B-Cell NHL or ALL | Anti-CD19 CAR-T/EGFRt +Cyclophosphamide +Fludarabine | I | Recruiting | Fred Hutchinson Cancer Research Center | To study the side effects of CAR-T cells | ||
NCT03085173 | R/R CLL | Anti-CD19 CAR-T/EGFRt | I | Recruiting | Memorial Sloan Kettering Cancer Center | To study the MTD of CAR-T cells | ||
CD123 | NCT02159495 | CD123+ R/R AML and persistent/recurrent BPDCN | Anti-CD123 CAR-T/EGFRt +Fludarabine | I | Recruiting | City of Hope Medical Center | To study the side effects and the best dose of CAR-T cells | |
NCT03114670 | Recurrent AML after allo-HSCT | Anti-CD123 CAR-T/EGFRt | I | Recruiting | Affiliated Hospital to Academy of Military Medical Sciences | To study the safety and effectiveness of CAR-T cells | ||
CD22 | NCT03244306 | CD22+ leukemia | Anti-CD22 CAR-T/EGFRt | I | Active, not recruiting | Seattle Children’s Hospital | To study the safety and feasibility of CAR-T cells | |
CD171 | NCT02311621 | Neuroblastoma | Anti-CD171 CAR-T/EGFRt | I | Recruiting | Seattle Children’s Hospital | To study the MTD of CAR-T cells | |
EGFR | NCT03618381 | R/R solid tumors | Anti-EGFR CAR-T/EGFRt | I | Recruiting | Seattle Children’s Hospital | To study the safety, feasibility, and efficacy of CAR-T cells | |
HER2 | NCT03500991 | HER2+ R/R pediatric CNS tumors | Anti-HER2 CAR-T/EGFRt | I | Recruiting | Seattle Children’s Hospital | To study the safety and feasibility of CAR-T cells via an indwelling CNS catheter | |
BCMA | NCT03070327 | Multiple myeloma | Anti-BCMA CAR-T/EGFRt +Cyclophosphamide +Lenalidomide | I | Recruiting | Memorial Sloan Kettering Cancer Center | To study the safety of CAR-T cells | |
iCasp9+ AP1903 | GD2 | NCT01822652 | Neuroblastoma | Anti-GD2 CAR-T/iCasp9 | I | Active, not recruiting | Baylor College of Medicine | To study the highest dose of CAR-T cells |
NCT01953900 | GD2+ osteosarcoma neuroblastoma | Anti-GD2 CAR-T/iCasp9 | I | Recruiting | Baylor College of Medicine | To study the largest safe dose of CAR-T cells | ||
NCT02107963 | GD2+ solid tumors | Anti-GD2 CAR-T/iCasp9 +Cyclophosphamide | I | Completed | National Cancer Institute | No results posted | ||
NCT03721068 | Neuroblastoma | Anti-GD2 CAR-T/IL-15/iCasp9 + Fludarabine +Cyclophosphamide | I | Recruiting | UNC Lineberger Comprehensive Cancer Center | To study the safety and feasibility of CAR-T cells | ||
CD19 | NCT03016377 | R/R ALL | Anti-CD19 CAR-T/iCasp9 +Cyclophosphamide +Fludarabine | I | Recruiting | UNC Lineberger Comprehensive Cancer Center | To study the safety and feasibility of CAR-T cells, and the optimal dose of AP1903 | |
NCT03696784 | R/R B-cell lymphoma | Anti-CD19 CAR-T/iCasp9 + Bendamustine +Fludarabine | I | Not yet recruiting | UNC Lineberger Comprehensive Cancer Center | To study the safety and feasibility of CAR-T cells | ||
CD19 CD22 | NCT03098355 | B-cell leukemia and lymphoma | Anti-CD19/22 CAR-T/iCasp9 + IL-2 | I/II | Recruiting | Zhujiang Hospital | To study the safety, efficacy and persistence of CAR-T cells | |
CD30 | NCT02274584 | CD30+ lymphomas | Anti-CD30 CAR-T/iCasp9 | I/II | Recruiting | Peking University | To study the safety of CAR-T cells | |
Mesothelin | NCT02414269 | Mesothelioma, lung cancer or breast cancer | Anti-mesothelin CAR-T/iCasp9 + Cyclophosphamide | I | Recruiting | Memorial Sloan Kettering Cancer Center | To study the safety of CAR-T cells | |
TanCAR | CD19 CD20 | NCT03019055 | R/R CD19+ or CD20+ B-cell malignancies | Anti-CD19/20 CAR-T cells | I/II | Recruiting | Medical College of Wisconsin | To study the safety and feasibility of CAR-T cells |
NCT03097770 | R/R B-cell leukemias and lymphomas | Anti-CD19/20-CAR-T cells | NA | Recruiting | Chinese PLA General Hospital | To study the safety and feasibility, and the duration of in vivo survival of tanCART-19/20 cells |
Safety strategy | Strengths | Weaknesses | |
---|---|---|---|
Suicide switch | HSV-TK | 1. powerful effect 2. extensive clinical experience | 1. immunogenicity 2. clinical incompatibility 3. slow onset 4. no preventive effect for toxicity 5. premature eradication of CAR-T cells |
iCasp9 | 1. no immunogenicity 2.clinical compatibility 2. rapid onset | 1. no preventive effect for toxicity 2. premature eradication of CAR-T cells | |
CD20 | 1. no immunogenicity 2. rapid onset | 1. antibody biodistribution 2. on-target toxicity from antibody 3. prodrug infusion reaction 4. no preventive effect for toxicity 5. premature eradication of CAR-T cells | |
EGFRt | 1. no immunogenicity 2. rapid onset 3. in vivo tracking | 1. antibody biodistribution 2. on-target toxicity from antibody 3. prodrug infusion reaction 4. no preventive effect for toxicity 5. premature eradication of CAR-T cells | |
Endogenous switch | synNotch | 1. control the expression of the CARs 2. Specific recognition of tumor sites | 1. uncontrolled activation of CAR-T cells 2. the choice of two antigens is difficult |
iCAR | 1. antigen-selectively regulate T cell responses 2. protect normal tissue from CAR-T cells | 1. uncontrolled activation of CAR-T cells 2. potential “on-target, off-tumor” effect | |
Combinatorial Target-Antigen Recognition | 1. precise killing of CAR-T cells 2. overcome antigen loss | 1. uncontrolled activation of CAR-T cells 2. the choice of two antigens is difficult 3. potential “on-target, off-tumor” effect | |
Exogenous switch | Bispecific T Cell Engager | 1. controlled activation of CAR-T cells 2. simplify manufacturing of CAR-T cells | 1. The choice of small molecules needs more consideration |
On-switch CAR | 1. controlled activation of CAR-T cells | 1. The choice of small molecules needs more consideration |