Table 2.
Selected clinical trials using CAR-T ACT therapy in NSCLC
| Target and its overexpression prevalence in NSCLC | NCT# | Phase | Population | Other information | Sponsor |
|---|---|---|---|---|---|
|
CLDN6 40% [27] |
NCT04503278 | I/II | Solid tumors, including NSCLC, CLDN6+ (≥ 50% of tumor cells expressing ≥ 2+ CLDN6 protein by IHC) | CLDN6 CAR-T with or without CLDN6 RNA-LPX cancer vaccine | BioNTech Cell & Gene Therapies GmbH |
|
CEA 50% [28] |
NCT04348643 | I/II | Solid tumors, including NSCLC, CEA+ (by IHC) or serum CEA level >50 ng | Chongqing Precision Biotech Co., Ltd | |
| NCT05736731 | I | Solid tumors, including NSCLC, CEA+ (by IHC), and HLA-A*02 loss | Autologous logic-gated Tmod™ CAR-T cell product | A2 Biotherapeutics Inc | |
|
EGFR 40–90% [29] |
NCT01869166 | I | NSCLC, EGFR+ (>50% IHC expression) | Autologous lentivirus transduced CAR-T cells | Chinese PLA General Hospital |
| NCT03182816 | I | NSCLC, EGFR+ (>50% IHC expression) | Autologous piggyBac transposon system generated CAR-T cells; second part with anti-PDL1 and anti-CTLA4 secreting EGFR CAR-T cells | NCT03182816 | |
| NCT05060796 | I | NSCLC, EGFR+ (≥2+ by IHC); CXCL13 factor positive rate ≥ 10% | CXCR5 modified EGFR CAR-T cells | Second Affiliated Hospital of Guangzhou Medical University | |
|
GPC3 55% SCC [30] |
NCT05120271 | I/II | SCC-NSCLC with GPC3 overexpression (by IHC) | SOTIO, LLC | |
|
ROR1 60% [31] |
NCT02706392 | NSCLC, ROR1+ (>20% by IHC) | Autologous 41BB CAR-T | Fred Hutchinson Cancer Center | |
| NCT05274451 | I | NSCLC, ROR1+ (by IHC) | Lyell Immunopharma, Inc. | ||
| MSLN 30–70% AC [32] | NCT02414269 | I/II | NSCLC metastatic to the pleura, MSLN+ (>10% by IHC), or elevated serum SMRP levels (>1.0 nM/L) | Intrapleural injection of iCasp9M28z CAR-T cells | Memorial Sloan Kettering Cancer Center |
|
B7H3 35% [33] |
NCT05190185 | I | NSCLC, B7H3+ (≥1% by IHC) | PersonGen BioTherapeutics (Suzhou) Co., Ltd. | |
| Several (HER2 13–20% [34], MSLN, MUC1, GPC3, EGFR, B7-H3) | NCT03198052 | I | Solid tumors, including NSCLC, target-positive (by IHC) | Autologous transduced T cells with > 20% expression of target-antigen CAR determined by flow cytometry and killing of target-positive cells > 20% in cytotoxicity assay | Second Affiliated Hospital of Guangzhou Medical University |
CAR chimeric antigen receptors, ACT adoptive cell therapy, NSCLC non-small cell lung carcinoma, CLDN6 Claudin-6, IHC immunohistochemistry, CEA carcinoembryonic antigen, HLA human leucocyte antigen, EGFR epithelial growth factor receptor, PDL1 programmed cell death lidang-1, CTLA4 cytotoxic T-lymphocyte-associated protein 4, CXCR C-X-C motif chemokine receptors, GPC3 Glypican 3, ROR1 retinoic acid-related orphan receptor-1, SCC squamous cell carcinoma, MSLN mesothelin, AC adenocarcinoma, SMRP soluble mesothelin-related peptides, HER2 human epidermal growth factor receptor-2, MUC1 Mucin-1