Table 2.
Types of scFv-based cancer treatments reported at ClinicalTrials.gov, accessed on 20 January 2023.
| Kind/Treatment Name | Description | Clinical Phase | Evidence |
|---|---|---|---|
| L19-IL2 is a tumor-directed immunocytokine consisting of IL2 and scFv directed against the ED-B domain of fibronectin. | Advanced solid tumors. | I/II | Register: NCT01058538 [106]. |
| Blinatumomab. | Relapsed or refractory B-cell precursor Philadelphia chromosome-negative acute lymphoblastic leukemia (R/R ALL). | Approved | Register: BLA 125557 [102]. |
| CAR-T cells, where the CAR consists of a scFv directed against CD19, with three intracellular signaling domains derived from CD3 zeta, CD28, and 4-1BB. | B cell lymphoma B cell leukemia. |
I/II | Register: NCT02132624 [107]. |
| CAR-T cells targeted to CD19 by a humanized scFv. | B-cell chronic lymphocytic leukemia treatment. | I/II | Register: NCT02782351 [108]. |
| Moxetumomab pasudotox. | Hairy cell leukemia. | Approved | Register: 1020748-57-5 [105]. |
| CAR-T cells expressing an anti-CD19 scFv bound to TCRζ and 4-1BB signaling domains. | Multiple myeloma. | I | Register: NCT02135406 [109]. |
| CAR-T cells expressing scFv with 41BB costimulatory domain and CD3ζ signaling domain targeting mesothelin or CD19. | Pancreatic cancer. | I | Register: NCT03497819 [110]. |
| CAR-T cells expressing an anti-CD19 scFv. | B-cell acute lymphocytic leukemia B-cell chronic lymphocytic leukemia B cell lymphoma. |
I | Register: NCT03685786 [111]. |
| CART-19 cells transduced with a lentiviral vector to express anti-CD19 scFv. | Patients With B Cell ALL, Relapsed or Refractory, With no Available Curative Treatment Options. | II | Register: NCT02030847 [112]. |
| Combination of radiotherapy with Darleukin, which is a fusion protein L19-IL2, composed of two fractions: L19, a scFv, linked by a flexible linker to IL2. | Stage IV non-small cell lung cancer. | II | Register: NCT03705403 [113]. |
| Autologous T cells expressing anti-CD19 scFv chimeric antigen receptors. | B cell neoplasms, B cell lymphoma, B-cell acute lymphoblastic leukemia. |
I | Register: NCT03559439 [114]. |
| CAR-T cells expressing anti-PD-L1 scFv. | Advanced lung cancer. | I | Register: NCT03330834 [115]. |
| CAR-T cells expressing an anti-CD276 scFv. | Solid tumors. | -- | Register: NCT04691713 [116]. |
| Autologous T cells expressing an anti-BCMA scFv coupled to TCRζ and 4-1BB signaling domains. | Multiple myeloma | I | Register: NCT02546167 [117]. |
| CAR T cells expressing anti-BCMA scFv. | Multiple myeloma | I | Register: NCT04650724 [118]. |
| CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv. | Leukemia, Acute Lymphoblastic. | II | Register: NCT02935543 [119]. |
| TILs/CAR-TILs with PD1 knockout and Anti-PD1/CTLA4-scFv Secreting or CARs. | Solid tumors such as liver, breast, lung, colorectal, and brain. | I | Register: NCT04842812 [120]. |
| CAR-T cells expressing scFv with affinity for malignant tumors. | Malignant tumors in children. | I | Register: NCT04691349 [121]. |
| Autologous T cells expressing scFv with specificity against GFRα4. | Recurrent or metastatic medullary thyroid cancer. | I | Register: NCT04877613 [122]. |
| CART-meso cells expressing an anti-mesothelin scFv fused with TCRζ and 4-1BB costimulatory domains. | Pancreatic cancer. | -- | Register: NCT03638193 [123]. |
| CAR T cells (huMNC2-CAR44) that bind via a scFv to the extracellular domain of the cleaved form of MUC1 (called MUC1*). | Metastatic breast cancer. | I | Register: NCT04020575 [124]. |
| CAR-T cells secreting scFv against OX40. | Lung cancer, hepatocellular carcinoma and solid tumor. |
I | Register: NCT04952272 [125]. |
| CAR-T cells that express scFv’s against PD1/CTLA4/Tigit. | Lung cancer. | I | Register: NCT03198052 [126]. |
| CAR-T cells with Ibalizumab-derived anti-CD4 scFv and the intracellular domains of CD28 and 4-1BB coactivators fused with the CD3ζ T cell activation signaling domain. | T cell lymphoma. T cell leukemia. |
I | Register: NCT03829540 [127]. |
| CAR-T cells expressing an anti-BCMA scFv. | Multiple myeloma. | I/II | Register: NCT05066646 [128]. |
| Autologous T cells expressing an anti-PSMA scFv, CD2 costimulatory domain, and dual-shielded with a dominant TGFβ receptor-negative domain and PD1.CD28 switch. | Metastatic prostate cancer. | I/II | Register: NCT05489991 [129]. |
| AR-NK cells that express and secrete IL7/CCL19 and/or scFv against PD1/CTLA4/Lag3, targeting Claudin 6. | Stage IV Ovarian Cancer Treatment. Refractory testicular cancer. Recurrent endometrial cancer. |
I/II | Register: NCT05410717 [130]. |
| Autologous T cells containing anti CD19 and anti CD20 scFv coupled to CD3ζ and co-stimulatory domain 4-1BB (4-1BB). | Non-Hodgkin’s lymphoma. B cell lymphoma. Chronic lymphocytic leukemia. Small lymphocyte lymphoma. |
I | Register: NCT03019055 [131]. |
| Tetravalent IgG(H)-scFv fusion-type of bi-specific antibody (BsAb). | Solid tumor. Advanced cancer metastatic cancer. Gastric cancer. Gastroesophageal junction carcinoma adenocarcinoma of the esophagus. Pancreatic ductal adenocarcinoma. |
I | Register: NCT04900818 [132]. |
| D2C7-IT is an immunotoxin composed of a scFv with high affinity for EGFRwt and EGFRvIII. | Malignant glioma recurrent brain tumor |
I | Register: NCT02303678 [133]. |
| L19TNF is a fully human fusion protein consisting of human TNF-α fused to the L19 antibody in scFv format, specific for the extra B domain of fibronectin. | Glioblastoma. | I/II | Register: NCT04573192 [134]. |
| CAR-T cells expressing an anti-GPRC5D scFv. | Relapsed/Refractory Multiple Myeloma Plasma cell leukemia. |
I | Register: NCT05219721 [135]. |
| BRITE is a bispecific hooker that has one scFv binding for the CD3 epsilon subunit while another scFv is directed against the hEGFRvIII epitope that is differentially expressed on the surface of tumor cells. | Malignant glioma Glioblastoma. |
I | Register: NCT04903795 [136]. |
| CAR-T cells expressing an scFv that recognizes CD19 and dual co-stimulating intracellular signaling domains (4-1BB and CD3ζ). | Recurrent Non-Hodgkin’s lymphoma. relapsed adult ALL. Recurrent Pediatric ALL. |
I/II | Register: NCT03938987 [137]. |
| Autologous Lymphoma Ig-derived scFv-chemokine DNA Vaccine. | Lymphoplasmacytic Lymphoma. | I | Register: NCT01209871 [138]. |
| T cells expressing anti-CD123 scFv chimeric antigen receptors linked to TCRζ and 4-1BB signaling domains. | Acute myeloid leukemia, relapsed. Acute myeloid leukemia, pediatric. Refractory acute myeloid leukemia. |
I | Register: NCT04678336 [139]. |
4-1BB: Cluster of differentiation 137; TILs: Tumor infiltration lymphocytes; IL2: Interleukin 2; PSMA: Tumor antigen prostate specific membrane antigen.