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. 2023 Feb 15;9(7):eadf3700. doi: 10.1126/sciadv.adf3700

Table 1. List of published TCR-T cell clinical trials.

Symbols: (), response duration in months after treatment; +, ongoing. Abbreviations: TDAs, tissue differentiation antigens; CGAs, cancer germline antigens; CR, complete response; PR, partial response by RECIST criteria; CEA, carcinoembryonic antigen; gp100, glycoprotein 100; HPV, human papillomavirus; MAGE-A, melanoma-associated antigen; MART-1, melanoma antigen recognized by T cells 1; NY-ESO-1, New York esophageal squamous cell carcinoma-1; MPNST, malign peripheral nerve sheath tumors; NSCLC, non–small cell lung cancer; CRS, cytokine release syndrome; n.s., not specified; KO-KI, knockout–knock-in; N.A., not available.

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%)