Table 2.
Summary of clinical trials exploiting the improvement strategy to overcoming CAR T cell challenges in solid tumors (from clinicalTrials.gov)
| Improving plan | Strategy | CAR T design | NCT number | Tumor type |
|---|---|---|---|---|
| Immune checkpoint inhibition | Expressing immune checkpoint antibodies | Anti-CTLA-4/PD-1 expressing MUC1-CAR-T | NCT03179007 | Advanced Solid tumor |
| Use CRISPR-Cas9 to knocked out the PD-1 gene | Mesothelin-directed CAR-T cells | NCT03747965 | Solid Tumor, Adult | |
| Secretion of anti-PD-L1 scFv | Autologous aPD-L1 armored anti-CD22 CAR T cells | NCT04556669 | Solid Tumor, Adult | |
| Cervical Cancer | ||||
| Sarcoma, NSCLC | ||||
| Secreting PD-1 nanobodies | αPD1-MSLN-CAR T cells | NCT04503980 | Colorectal Cancer | |
| Ovarian Cancer | ||||
| Pembrolizumab | CART-EGFRvIII T cells | NCT03726515 | Glioblastoma | |
| Ipilimumab, | IL13Rα2-Targeted CAR-T Cells | NCT04003649 | Recurrent Glioblastoma | |
| Nivolumab | Refractory Glioblastoma | |||
| Cytokine secretion | IL-15 | Glypican-3-specific CAR-T Cells | NCT04377932 | Liver Cancer, Wilms Tumor, Yolk Sac Tumor, Liposarcoma, and 2 more |
| IL-15 and IL-21 | Glypican-3-specific CAR-T Cells | NCT04715191 | Liver Cancer, Wilms Tumor, Yolk Sac Tumor, Liposarcoma, and 2 more | |
| IL-12 | 4H11-28z/fIL-12/EGFRt + Genetically-modified T cells | NCT02498912 | Solid Tumors | |
| Lymphodepletion | Cyclophosphamide | Anti-GD2-CAR engineered T cells | NCT02107963 | Sarcoma, Osteosarcoma |
| Neuroblastoma, Melanoma | ||||
| Fludarabine, Cyclophosphamide | Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs | NCT03084380 | Hepatocellular Carcinoma | |
| Transient CAR expression | RNA electroporation | T cells modified with RNA anti -cMET CAR | NCT03060356 | Malignant Melanoma, |
| Breast Cancer | ||||
| Diminishing toxicity and CRS | AP1903 | Anti-GD2-CAR engineered T cells | NCT02107963 | Sarcoma, Osteosarcoma |
| Neuroblastoma, Melanoma | ||||
| Metoprolol, a beta-blocker | CAR T cells | NCT04082910 | Solid Tumor, | |
| Hematological Malignancy | ||||
| Inducible caspase 9 safety switch | iC9.GD2.CAR.IL-15 T-cells | NCT03721068 | Neuroblastoma, | |
| Osteosarcoma | ||||
| Improving cell proliferation and persistence | Aldesleukin | Anti-hCD70 CAR transduced PBL | NCT02830724 | Pancreatic Cancer, Renal Cell Cancer, Breast Cancer |
| Melanoma, Ovarian Cancer | ||||
| Rimiducid (improved by activating the iMC) | PSCA-Targeted CAR-T Cells (BPX-601) | NCT02744287 | Metastatic Prostate Cancer | |
| Metastatic Pancreatic Adenocarcinoma, and 3 more |
Programmed cell death protein 1 (PD1), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), Mucin 1 (MUC1), Clustered regularly interspaced short palindromic repeats (CRISPR), CRISPR-associated protein 9 (Cas9), Single chain variable fragment (scFv), Non-small cell lung cancer (NSCLC), Mesothelin (MSLN), Epidermal growth factor receptor variant III (EGFRvIII), Glypican-3 (GPC3), Inducible caspase 9 (iC9), Peripheral blood lymphocytes (PBL), Prostate stem cell antigen (PSCA)