Table 3.
Systems for controlling transgene expression applied to immunotherapy.
| System | Inductor | Gene | Model/Disease | Product | Administration | Clinical stage | Ref |
|---|---|---|---|---|---|---|---|
| Tet-On 3G (TaKaRa Bio) |
Dox | CAR-CD19 | CD19+ Raji cells (Burkitt's lymphoma) |
All-in-one RV-T cells |
Cellsa: intravenously Inductor: pre-induced ex vivo+ oral |
Pre-clinical | (22) |
| Tet-On (Sangon Biotech) |
Dox | CAR-CD19 | CD19+ Raji cells (Burkitt's lymphoma) |
All-in-one LV-T cells |
In vivo experiments were not conducted | In vitro | (23) |
| Tet-On 3G (Clontech) |
Dox | CAR-CD38 | CD38+ cell lines (Multiple myeloma) |
Dual system RV-T cells |
in vivo experiments were not conducted | In vitro | (24) |
| Tet-On 3G (TaKaRa Bio) |
Dox | CAR-CD147 | CD147+ cells (Hepatocellular carcinoma) | All-in-one LV-T cells |
Cellsa: intratumoral Inductor: pre-induced ex vivo |
Pre-clinical | (26) |
| Tet-On | Dox | IL-10 | DBA1 mice (Rheumatoidarthritis) |
All-in-one AAV vp |
Vectorb: intramuscularly Inductor: oral |
Pre-clinical | (46) |
| Tet-On | Dox | FLT3L | Glioblastoma multiforme | All-in-one Ad |
Vectorb: intracranial Inductor: oral |
Phase I | (47) |
| RheoSwitch (RTS) |
Veledimex | IL-12 | Stage III or IV melanoma | All-in-one Ad-DCs |
Cellsa: intratumoral Inductor: oral |
Phase I | (57) |
| RheoSwitch (RTS) |
Veledimex | IL-12 | Stage III-IV melanoma Metastatic breast cancer | All-in-one AdV |
Vectorb: accessible lesions Inductor: oral |
Phase I/II | (56) |
| Gene Switch | MFP | IL-12 | MC-38 mice (Livermetastases) | All-in-one AdV |
Vectorb: intravenous Inductor: intraperitoneal |
Pre-clinical | (68) |
| Gene Switch | MFP | IFN-β | EAE mice (multiple sclerosis) | DNA plasmid |
Plasmidc: intramuscular Inductor: subcutaneous |
Pre-clinical | (74) |
| Light- pNFAT | Blue light | IL-2, IL-15, TNF-α |
SK-HEP-1 mouse (Hepatocellular carcinoma) | All-in-one LV-T cells |
Cellsa: subcutaneous Inductor: externally applied |
Pre-clinical | (80) |
| LINTAD | Blue light | CAR-CD19 | CD19+ Nalm6+ mice (B-lymphoblastic leukemia) | Dual system LV-T cells |
Cellsa: subcutaneous Inductor: externally applied |
Pre-clinical | (81) |
| TNFerade | Radiation | TFN-a | Metastatic pancreatic cancer | All-in-one Deficient AdV |
Vectorb: intratumor Inductor: externally applied |
Phase III | (82) |
| FUS-CAR | Ultra-sounds | CAR-CD19 | CD19+ Nalm6+ cells (B-lymphoblastic leukemia) PC3 cells (Prostatecancer) | Dual system LV-T cells |
Cellsa: subcutaneous Inductor: externally applied |
Pre-clinical | (83) |
a
Ex vivo transduction.
b
in vivo transduction.
c
Direct plasmid injection Dox, doxycycline; MFP, mifepristone; CAR, chimeric antigen receptor; IL-10, interleukin 10; FLT3L, FMS-like tyrosine kinase 3 ligand; IL-12, interleukin 12; IFN-β, interferonβ; IL-2, interleukin 2; IL-15, interleukin 15; TNF-α, tumor necrosis factor α; EAE, experimental autoimmune encephalomyelitis; RV, retroviral vector; LV, lentiviral vector; AAV, Adeno-associated vector; vp, viral particles; Ad, adenoviral vector; Ref, reference.