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Table 2 Summary of clinical trials exploiting the improvement strategy to overcoming CAR T cell challenges in solid tumors (from clinicalTrials.gov)

From: Hurdles to breakthrough in CAR T cell therapy of solid tumors

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
  1. 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)