Table 5.
Published clinical targets of CAR-T therapy for solid tumors.
| Target | Disease | Costimulatory domain | Vector | Pretreatment | Dose | No. of patients | Phage | Response | Country | References |
|---|---|---|---|---|---|---|---|---|---|---|
| EGFRvIII | Glioblastoma | 4-1BB | Lentivirus | Temozolomide radiation | 1–5 × 108/person | 10 | I | 5 remission | United States | (43) |
| EGFR | NSCLC | 4-1BB | Lentivirus | CY, CDDP | 4.5 × 106−1.09 × 107/kg | 11 | I/II | 7/11 remission; | China | (83) |
| GD2 | NB | NA | Retrovirus | – | 2 × 107−1 × 108/m2 | 19 | I | 11/19 remission | United States | (84) |
| GD2 | Metastatic melanoma | CD28 + OX40 | Retrovirus | FLU, CY | 1–2 × 107/m2 | 4 | I | 4 partial response | South Australia | (85) |
| IL13Rα2 | GBM | NA | DNA electroporation | – | 10.6 × 108/person | 13 | I | 3 relapse | United States | (86) |
| IL13Rα2 | GBM | 4-1BB | Lentivirus | – | Total dose of 5.2–9.2 × 107/person | 1 | I | 1 relapse | United States | (87) |
| HER2 | PNET; DSRCT | CD28 | Retrovirus | Chemotherapy | 1 × 104−1 × 108/m2 | 19 | I/II | 1 necrosis; 4/19 remission; | United States | (88) |
| CAIX | RCC | NA | Retrovirus | – | 3 × 108−2.1 × 109/person | 11 | – | – | Netherlands | (89) |
| CAIX | RCC | NA | Retrovirus | – | 6 × 108−4 × 109/person | 12 | – | – | Netherlands | (90) |
| Mesothelin | PAC; MPM | 4-1BB | mRNA electroporation | – | Total dose of 1.2 × 109/person | 4 | – | 1 allergic reactions and cardiac arrest | United States | (91) |
| Mesothelin | MPM; PDA | 4-1BB | mRNA electroporation | Chemotherapy | 4.4 × 109 of one patient; 3.1 × 109/m2 of another | 2 | I | 1 partial response | United States | (92) |
| MUC1 | Seminal vesicle cancer | CD28 + 4-1BB | Lentivirus | – | Intratumoral injection of 5 × 105 cells at two sites, respectively | 1 | I | no side effects | China | (93) |
| CEA | mCRC | CD28 | Lentivirus | CY, FLU | 2.5 × 107-1.52 × 1010/person | 10 | I | 70% remission | China | (44) |
| CEA | Liver metastases | CD28 | Retrovirus | – | 1 × 108−3 × 1010/person | 6 | I | 5 patients died of progressive disease; | United States | (94) |
| CEA | Adenocarcinoma; PMP | NA | – | FLU, CY | 1 × 109−5 × 1010/person | 14 | I | Transient acute respiratory toxicity | United Kingdom | (40) |
| BCMA | MM | CD28 | Retrovirus | CY, FLU | 3 × 105−9 × 106/kg | 12 | I | 1 relapse after 17 weeks; 1 complete remission | United States | (95) |
| c-Met | Breast cancer | 4-1BB | mRNA electroporation | – | 3 × 107−3 × 108/person | 6 | – | Tumor necrosis at the injection site | United States | (96) |
| PSMA | PCa | NA | Retrovirus | Chemotherapy | 1 × 109−1 × 1010/person | 5 | I | 2/5 partial remission | United States | (97) |
| TAG72 | CRC | NA | Retrovirus | – | 3−3.11 × 1010/person | 16 | I | Low-grade CRS | United States | (98) |
CDDP, cis-diamminedichoro platinum; NB, neuroblastoma; GBM, glomerular basement membrane; PNET, primitive neuroectodermal tumors; DSRCT, desmoplastic small round cell tumor; PAC, perennial allergic colitis; MPM, malignant pleural mesothelioma; PDA, patent ductus arteriosus; mCRC, metastatic colorectal cancer; PMP, pseudomyxoma peritonei; MM, multiple myeloma; PCa, prostate cancer; CRC, colorectal cancer; CAIX, carbonic anhydrase IX, c-Met, c-mesenchymal–epithelial transition; PSMA, prostate-specific membrane antigen; TAG72, tumor-associated glycoproteins-72; NA, not applicable. The first generation of CAR contains a CD3 signaling domain.