Table 1. List of published TCR-T cell clinical trials.
Antigen type | Target antigen | Epitope | HLA | Cancer type | Vector | Number of cells | Number of patients | Clinical trial | Phase | Objective response rate (ORR) (%) | Clinical response (months) | Toxicities related to TCR-T cells (%) | Reference |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
TDAs | MART-1 | AAGIGILTV | HLA-A*02:01 | Melanoma | Retrovirus | 0.5 to 34 × 109 | 17 | n.s. | n.s. | 2 (12%) | 2 PR (20, 21) | None | Morgan et al. (10) |
MART-1 | AAGIGILTV | HLA-A*02:01 | Melanoma | Retrovirus | 0.15 to 10 × 1010 | 20 | NCT00509288 | II | 6 (30%) | 6 PR (3, 4, 9, 17+, 17+) | Skin rash: 14 (70%) | Johnson et al. (11) | |
Uveitis: 11 (55%) | |||||||||||||
Hearing loss: 10 (50%) | |||||||||||||
MART-1 | EAAGIGILTV | HLA-A*02:01 | Melanoma | Retrovirus | 0.6 to 4.8 × 109 | 13 | NCT00910650 | II | 0 | Skin rash: 3 (23%) | Chodon et al. (12) | ||
CRS: 2 (15%) | |||||||||||||
MART-1 | EAAGIGILTV | HLA-A*02:01 | Melanoma | Retrovirus | 0.05 to 4.56 × 109 | 12 | NCT02654821 | I/IIa | 2 (16.7%) | 2 PR (4.1, 7.1) | CRS/sepsis: 1 (8%) | Rohaan et al. (13) | |
Dermatitis: 10 (83%) | |||||||||||||
Uveitis: 2 (17%) | |||||||||||||
Hearing loss: 4 (33%) | |||||||||||||
gp100 | KTWGQYWQV | HLA-A*02:01 | Melanoma | Retrovirus | 0.18 to 11 × 1010 | 16 | NCT00509496 | II | 3 (16%) | 1 CR (14+) | Skin rash: 15 (94%) | Johnson et al. (11) | |
Uveitis: 4 (25%) | |||||||||||||
2 PR (4, 3) | Hearing loss: 5 (31%) | ||||||||||||
CEA | IMIGVLVGV | HLA-A*02:01 | Colorectal cancer | Retrovirus | 2 to 4 × 108 | 3 | NCT00923806 | I | 1 (33%) | 1 PR (6) | Severe transient colitis: 3 (100%) | Parkhurst et al. (14) | |
CGAs | MAGE-A3 | KVAELVHFL | HLA-A*02:01 | Melanoma | Retrovirus | 2.8 to 7.9 × 1010 | 9 (7 + 1 + 1) | NCT01273181 | I/II | 5 (56%) | 1 CR (15+) | Severe neurologic toxicity: 3 (33%) including 2 deaths | Morgan et al. (16) |
Synovial sarcoma | 4 PR (4, 4, 5, 12+) | ||||||||||||
Esophageal cancer | |||||||||||||
MAGE-A3 | EVDPIGHLY | HLA-A*01 | Melanoma | Lentivirus | 2.4 to 5.3 × 109 | 2 (1 + 1) | NCT01350401 | I | 0 | Severe cardiac toxicity and death: 2 (100%) | Linette et al. (17) | ||
Myeloma | NCT01352286 | ||||||||||||
MAGE-A3 | HLA-DPB1*0401 | Metastatic solid tumors | Retrovirus | 0.01 to 123 × 109 | 17 | NCT02111850 | I | 4 (23.5%) | 1 CR (29+) 3 PR (4, 4, 18+) | Liver toxicity: 2 (12%) | Lu et al. (18) | ||
MAGE-A4 | NYKRCFPVI | HLA-A*24:02 | Esophageal cancer | Retrovirus | 0.2 to 5 × 109 | 10 | UMIN000002395 | I | 0 | none | Kageyama et al. (19) | ||
MAGE-A4 | GVYDGREHTV | HLA-A*02 | Advanced solid tumors | Lentivirus | 0.12 to 10 × 109 | 38 | NCT03132922 | I | 9 (23.7%) | 9 PR | CRS: 9 (50%) | Hong et al. (20) | |
MAGE-A10 | GLYDGMEHL | HLA-A*02:01 or HLA-A*02:06 | NSCLC | Lentivirus | 0.1 to 6.77.109 | 11 | NCT02592577 | I | 1 (9%) | 1 PR (1) | CRS: 3 (27%) | Blumenschein et al. (21) | |
Neurotoxicity: 1 (9%) | |||||||||||||
NY-ESO-1 | SLLMWITQC | HLA-A*02:01 | Melanoma | Retrovirus | 0.16 to 13 × 1010 | 17 (11 + 6) | NCT00670748 | I | 5 (45%) 4 (67%) | 2 CR (20+, 22+) | None | Robbins et al. (22) | |
Synovial sarcoma | 3 PR (3, 8, 9+) | ||||||||||||
4 PR (5, 8, 10, 18) | |||||||||||||
NY-ESO-1 | SLLMWITQC | HLA-A*02:01 | Melanoma | Retrovirus | 0.9 to 13 × 1010 | 38 (20 + 16) | NCT00670748 | II | 11 (55%) 11 (61%) | 4 CR (24, 40+, 54+, 58+) | None | Robbins et al. (23) | |
7 PR (3, 3, 5, 6+, 8, 10, 28) | |||||||||||||
Synovial sarcoma | 1 CR (6) | ||||||||||||
10 PR (3, 3, 4, 5, 7, 8, 10, 11, 18, 47+) | |||||||||||||
NY-ESO-1 | SLLMWITQC | HLA-A*02:01 | Melanoma | Retrovirus | 1 × 109 | 10 | NCT02070406 | I | 2 (20%) | 2 PR | CRS: 1 (10%) | Nowicki et al. (24) | |
Synovial sarcoma | |||||||||||||
Liposarcoma | NCT01697527 | ||||||||||||
Osteosarcoma | |||||||||||||
MPNST | |||||||||||||
NY-ESO-1 | SLLMWITQC | HLA-A*02:01 HLA-A*02:06 | Synovial sarcoma | Lentivirus | 0.4 to 14.4 × 109 | 12 | NCT01343043 | I/II | 6 (50%) | 1 CR (8) | CRS: 5 (42%) | D’Angelo et al. (25) | |
5 PR (4, 7, 8, 18) | |||||||||||||
NY-ESO-1SLLMWITQC | HLA-A*02:01 HLA-A*02:06 | Synovial sarcoma | Lentivirus | 2.67 × 109 | 30 | NCT01343043 | I/II | 9 (30%) | 9 PR (2-13) | n.s. | Ramachandran et al. (26) | ||
NY-ESO-1(CRISPR -Cas9)SLLMWITQC | HLA-A*02:01 | Liposarcoma Myeloma | Lentivirus | 0.6 to 7.1 × 108 | 3 | NCT03399448 | I | 0 | None | Stadtmauer et al. (27) | |||
Viral antigens | HPV16-E6 | TIHDIILECV | HLA-A*02:01 | HPV16-positive epithelial cancer | Retrovirus | 0.1 to 13.4 × 1010 | 12 | NCT02280811 | I/II | 2 (17%) | 2 PR (3, 6) | None | Doran et al. (38) |
HPV16-E7 | YMLDLQPET | HLA-A*02:01 | HPV16-positive epithelial cancer | Retrovirus | 0.1 to 12.1010 | 12 | NCT02858310 | I | 6 (50%) | 6 PR (3, 4, 4, 8, 8, 9) | None | Nagarsheth et al. (39) | |
HBV | N.A. | HLA-A*02 or HLA-Cw0801 | HBV-HCC | Electroporation | 1 × 104/kg to 5 × 106/kg | 8 | NCT03899415 | I | 1 | 1 PR (27.7) | Liver toxicity: 1 (12%) | Meng et al. (40) | |
MCPyV | KLLEIAPNC | HLA-A*02:01 | Merkel cell carcinoma | Lentivirus | 1 to 9 × 108 | 5 | NCT03747484 | I | 1 (25%) | n.s. | None | Veatch et al. (41) | |
Neo-antigens | TP53 | HMTEVVRHC | HLA-A*02:01 | Metastatic breast cancer | Retrovirus | 5.3 × 1010 | 1 | NCT03412877 | I | 1 (100%) | 1 PR (6) | CRS | Kim et al. (34) |
KRAS G12D | GADGVGKSA | HLA-C*08:02 | Metastatic pancreatic cancer | Retrovirus | 1.6.1010 | 1 | IND 27501 | I | 1 (100%) | 1 PR (6+) | None | Leidner et al. (35) | |
GADGVGKSAL | |||||||||||||
Mutation-associated neoantigens (CRISPR-Cas9 KO-KI) | Multiple HLA class I | Metastatic solid tumors | Electroporation | 0.13 to 4.109 | 16 | NCT03970382 | I | 0 | CRS: 1 (6%) | Foy et al. (37) | |||
Neurotoxicity: 1 (6%) |