Table 1.
Selected solid and hematological tumor targets other than CD19 that are currently being investigated as targets for CAR T cells.
| Target | Indication | Preclinical Antitumor Efficacy | Clinical Efficacy/Safety | Ongoing Trials |
|---|---|---|---|---|
| Solid tumor targets | ||||
| EGFRvIII (38, 70) | Glioma, glioblastoma, head and neck cancer | Human glioma cells in vitro and ex vivo, glioblastoma xenograft model | None reported |
NCT02209376 NCT01454596 |
| ERBB2 (42, 71, 72) | Glioblastoma, sarcoma | Tumor cell lines, breast cancer xenograft model | Stable disease for 12 weeks to 14 months in 24% of pts (n=17) |
NCT00902044 NCT01109095 NCT00889954 |
| Mesothelin (43, 62, 73, 74) | Mesothelioma, pancreatic cancer, ovarian cancer, lung cancer | Mesothelioma xenograft model | Stable disease in 67% of pts at day 28 (n = 6) |
NCT02159716 NCT02414269 NCT01583686 |
| Carbonic anhydrase IX (75, 76) | RCC | RCC cells in vitro | Liver toxicity affected several pts | None |
| PSMA (folate hydrolase 1) (40, 44) | Prostate cancer | Prostate adenocarcinoma murine model | Stable disease in 50% of pts treated (n = 4) | NCT01140373 |
| FAP (77-79) | Mesothelioma | Murine pancreatic cancer model, lung cancer xenograft model | None reported | NCT01722149 |
| Carcinoembryonic antigen (80) | Lung, colorectal, gastric, breast, and pancreatic cancers | Murine model of liver metastases | None reported | NCT02349724 |
| 5T4 (trophoblast glycoprotein) (81) | Solid tumors | Murine models of melanoma and colon carcinoma | None reported | None |
| Hematologic malignancy targets | ||||
| CD22 (82, 83) | B-ALL, B-NHL | B-ALL cell lines, xenograft model | MRD-negative CR in 29% of evaluable pediatric pts with ALL; CRS occurred in 57% of pts (n=7) |
NCT02315612 NCT02588456 |
| BCMA (TNFRSF17) (84, 85) | MM | MM primary cells and cell lines, xenograft model | ORR in 33% of pts (n=12) |
NCT02215967 NCT02546167 |
| CD123 (IL3RA) (86) | AML | Primary AML in immunodeficient mice | None reported |
NCT02159495 NCT02623582 |
| CS1 (SLAM7) (87) | AML, MM | Primary MM cells in vitro, MM xenograft model | None reported | NCT02203825 |
| CD138 (syndecan 1) (88) | MM | Primary MM cells in vitro, MM xenograft model | None reported | NCT01886976 |
| Kappa light chain of Ig (89) | MM, CLL, lymphoma | B-CLL cells in vivo and in vitro | None reported | NCT00881920 |
| ROR1 (90, 91) | Hematologic and solid tumors | Primary B-CLL and MCL cells in vitro, RCC cell lines, breast cancer cell lines | None reported | NCT02194374 |
AML, acute myeloid leukemia; BCMA, B-cell maturation antigen; CLL, chronic lymphocytic leukemia; CR, complete response; CRS, cytokine release syndrome; EGFRvIII, epidermal growth factor receptor vIII; FAP, fibroblast activation protein alpha; HPV, human papillomavirus; Ig, immunoglobulin; IL3RA, interleukin 3 receptor subunit alpha; MCL, mantle cell lymphoma; MM, multiple myeloma; MRD, minimal residual disease; NHL, non-Hodgkin lymphoma; ORR, overall response rate; PSMA, prostate-specific membrane antigen; RCC, renal cell carcinoma; ROR1, receptor tyrosine kinase-like orphan receptor 1; TCR, T-cell receptor.