Table 1.

Main clinical trials, based on adoptive transfer of engineered immune cells, including SyS patients in their cohorts.

Target Antigen	Trial Number	Study Description	Main Results and References
NY-ESO-1	NCT00670748	Pilot phase I study: NY-ESO-1 TCR-T-cells plus IL2 in heavily pretreated metastatic HLA-A*02-positive SyS patients with >50% expression of NY-ESO-1	ORR 61% objective clinical responses in 11/18 SyS patients [66]
	NCT01343043	Pilot phase I study: NY-ESO-1 TCR-T-cells plus IL2 in heavily pretreated metastatic HLA-A*02-positive SyS patients among four cohorts allocated between different levels of NY-ESO-1 expression and lympho-depletion regimens	ORR 20–50% [68,69,70,80]
	NCT03967223	Phase II study: First generation of NY-ESO-1 TCR-T-cells as a first line treatment in advanced metastatic, previously untreated HLA-A*02-positive patients with NY-ESO-1-positive SyS or MRCLS and as a second line treatment after first line anthracycline-based chemotherapy	Active, not recruiting [70]
	NCT04526509	Phase I master protocol of three different next generation NY-ESO-1 TCR-T-cell co-expressing CD8 alpha cell surface receptor, or co-expressing the dominant-negative TGF-beta receptor type II, or engineered using the epigenetically reprogrammed (Epi-R) manufacturing process	Active, not recruiting [70]
	NCT04939701	Phase I/II trial: Human artificial adjuvant vector cells (aAVC) loaded with the CD1d ligand alpha-galactosylceramide and modified to express NY-ESO-1 in combination with pembrolizumab for SyS, MRCLS, ovarian carcinoma, non-small cell lung cancer, and esophageal squamous cell carcinoma	Active, not recruiting [45]
MAGE-A4	NCT03132922	Phase I multi-tumor trial: Afami-cel (carrying TCR specific for a MAGE-A4230−239 peptide, GVYDGREHTV, presented by HLA-A*02) in HLA-A*02+ patients with advanced metastatic MAGE-A4-expressing solid tumors, across nine tumor types including SyS	ORR 44% for SyS and 9% for all other tumors [74]
	NCT04044768	Phase II SPEARHEAD-1 trial: A single arm open-label clinical trial on ADP-A2M4 SPEAR™ T-Cells in HLA-A*02 eligible and MAGE-A4 positive subjects with metastatic or inoperable SyS or MRCLS	ORR 40.7% in SyS [75,76]
PRAME	NCT03686124	The ACTENGINE IMA203/IMA203CD8 trial: TCR-T-cells directed against an HLA-A*02-restricted peptide derived from PRAME after lymphodepletion, with or without nivolumab in patients with advanced solid tumors	ORR 60% in SyS Objective clinical responses in 3/5 SyS patients [79]