Table 1.
Common solid tumor associated target antigens, most recent CAR constructs, and the stage of testing they have reached.
| Target TAA | Solid tumors expressing target TAA | Type of CAR | Clinical trials* | Phase |
|---|---|---|---|---|
| CD44v6 | (Metastasized) colon cancer, soft tissue sarcoma (STS), possible marker for many metastasizing tumors (12, 13) |
28ζ CAR-CIK/ HSV-TK suicide gene | Preclinical | – |
| CAIX (carbonic anhydrase IX) | Metastatic clear cell renal cell carcinoma (ccRCC) (14, 15) |
CD4TM-γ | Study stopped | I/II |
| CEA (carcinoembryonic antigen) | Ovarian, gastrointestinal, colorectal, hepatocellular carcinoma (HCC) (16–18) |
CD3ζ |
NCT02959151 NCT02850536 NCT02349724 NCT03267173 |
I/II Ib I Early I |
| CD133 | Ovarian, glioblastoma (GBM), HCC (17–19) |
BBζ – |
NCT02541370 NCT03423992 |
I/IIa I |
| c-Met (Hepatocyte growth factor receptor) | Breast (50%), melanoma, HCC (20) |
BBζ mRNA c-Met/PDL-1 |
NCT01837602 NCT03060356 NCT03672305 |
Early I Early I Early I |
| EGFR (epidermal growth factor receptor) | NSCLC, GBM, sarcoma, malignant pleural mesothelioma (MPM) (79.2%), retinoblastoma, glioma, medulloblastoma, osteosarcoma, Ewing sarcoma (21–23) |
28/BBζ α-CTLA-4/PD-1 IL12 BBζ/EGFR806/ tEGFR suicide gene |
NCT03152435 NCT03182816 NCT03542799 NCT03638167 NCT03618381 |
I/II I/II I I I |
| EGFRvIII (type III variant epidermal growth factor receptor) | GBM (24–67%), glioma, colorectal, sarcoma, pancreatic (16, 24) |
– tEGFR suicide gene – – BBζ+pembrolizumab – |
NCT03283631 NCT02844062 NCT01454596 NCT03267173 NCT03726515 NCT03423992 |
I I I/II Early I I I |
| Epcam (epithelial cell adhesion molecule) | HCC, lung, ovarian, colorectal, breast, gastric, stomach, esophogeal, pancreatic, liver, prostate, gynecological cancers, nasopharyngeal carcinoma (16, 25) |
– – 28ζ – – |
NCT02915445 NCT03563326 NCT03013712 NCT02729493 NCT02725125 |
I I I/II I/II I/II |
| EphA2 (Erythropoetin producing hepatocellular carcinoma A2) | GBM, glioma (26, 27) |
– | NCT03423992 | I |
| Fetal acetylcholine receptor | Osteosarcoma, rhabdomyosarcoma (28) | CD3ζ | Preclinical | – |
| FRα (folate receptor alpha) | Ovarian (90%), urothelial bladder carcinoma (14) |
4SCAR (4th gen) | NCT03185468 | II |
| GD2 (Ganglioside GD2) | Neuroblastoma, melanoma, osteosarcoma (100%), rhabdomyosarcoma (13%), Ewing's sarcoma (20%), cervical (29–32) |
3rd gen/inducible Caspase-9/IL-15 28ζ/OX40/iC9/VZV iC9 C7R (IL-7 receptor) 4SCAR – – – – 4SCAR/IgT |
NCT03721068 NCT01953900 NCT03373097 NCT03635632 NCT02765243 NCT02919046 NCT02761915 NCT03356795 NCT03423992 NCT03356782 |
I I I/II I II I/II I I/II I I/II |
| GPC3 (Glypican-3) | HCC, squamous cell carcinoma (SCC) (17) |
– BBζ/tEGFR – – – – BBζ 3rd gen – – |
NCT02959151 NCT03084380 NCT02932956 NCT02905188 NCT02876978 NCT02715362 NCT03130712 NCT03198546 NCT03146234 NCT03302403 |
I/II I/II I I I I/II I/II I N/A N/A |
| GUCY2C (Guanylyl cyclase C) | Metastatic colorectal (33) | ? | Preclinical | – |
| HER1 (human epidermal growth factor receptor 1) | Lung, prostate (1, 34) | Preclinical | – | |
| HER2 (human epidermal growth factor receptor 2) (ERBB2) | Breast (25–30%), ovarian (25–30%), osteosarcoma (60%), GBM (80%), medulloblastoma (40%), gastric, MPM (6.3%), sarcoma, pediatric CNS (23, 24, 35–38) |
BBζ/tCD19 – HER2-AdVST + oncolytic adenovirus – – 3rd gen 28ζ aE7 BBζ/tCD19 TCM – – |
NCT03696030 NCT02713984 NCT03740256 NCT02442297 NCT03500991 NCT03198052 NCT00902044 NCT03267173 NCT03389230 NCT03423992 NCT02792114 |
I I/II I I I I I Early I I I I |
| ICAM-1 (Intercellular adhesion molecule 1) | Thyroid (60%) (39, 40) |
3rd gen | Preclinical | |
| IL13Rα2 (interleukin 13 receptor α2) | Glioma, GBM (41, 42) |
–BBζ/tCD19 |
NCT03423992 NCT02208362 |
I I |
| IL11Rα (interleukin 11 receptor α) | Osteosarcoma (28) |
28ζ | Preclinical | |
| Kras (Kirsten rat sarcoma viral oncogene homolog) | Lung adenocarcinoma (30%), pancreatic (43) |
– | Preclinical | |
| Kras G12D | Pancreatic ductal adenocarcinoma (PDA), colorectal, lung (44) |
ACT | Clinical | |
| L1CAM (L1-cell adhesion molecule) | Ovarian (45) |
28ζ | Preclinical | |
| MAGE | NSCLC (MAGE-A3/6), metastatic melanoma (70% MAGE-A1-5) (46, 47) |
TCR-directed therapy | ||
| MET | MPM (67%) (48) |
28ζ | Preclinical | |
| Mesothelin | PDA (up to 100%), MPM (85%), Ovarian (70%), lung adenocarcinoma (53%, advanced; 69%, early stage), GBM (49–52) |
– ? PD-1/TCR KO αCTLA-4/PD-1 – αPD-1 PD-1 KO – αPD-1 – – BBζ 28ζ MCY-M11 |
NCT02930993 NCT02959151 NCT03545815 NCT03182803 NCT01583686 NCT03030001 NCT03747965 NCT03198052 NCT03615313 NCT03267173 NCT03356795 NCT02792114 NCT02414269 NCT03608618 |
I I/II I I/II I/II I/II I I I/II Early I I/II N/A I I |
| MUC1 (mucin 1) | HCC, NSCLC, pancreatic, breast, glioma, colorectal, gastric (17) |
αCTLA-4/PD-1 – ± PD-1 KO T cells ± PD-1 KO T cells – – – 4SCAR-IgT – |
NCT03179007 NCT02587689 NCT03706326 NCT03525782 NCT03198052 NCT03267173 NCT03356795 NCT03356782 NCT03633773 |
I/II I/II I/II I/II I Early I I/II I/II I/II |
| MUC16 ecto (mucin 16) | Ovarian (18, 53) |
TCR-directed CAR |
Clinical Preclinical |
|
| NKG2D (natural killer group 2 member D) | Ewing's sarcoma, osteosarcoma, ovarian (18, 54) | NK-CAR CAR |
Clinical Preclinical |
|
| NY-ESO-1 | Liposarcoma (>89%), neuroblastoma (82%), synovial sarcoma (80%), melanoma (46%), ovarian (43%), breast (46%), GBM, NSCLC (47, 55, 56) |
TCR-CARACT/TCR-directed therapies | Preclinical Clinical |
|
| PSCA (prostate stem cell antigen) | Pancreatic, prostate (57) |
– |
NCT03198052 NCT03267173 |
I Early I |
| WT-1 (Wilms tumor 1) | Ovarian (17) |
– | Preclinical |
*
Recruiting/not yet recruiting studies listed.