Table 5.

Summary of most recent advances in immunotherapy for the management of uveal melanoma.

Agent	Study Type	Main Findings	References
Checkpoint Inhibitors
Ipilimumab	N/A	At 3 mg/kg, overall response rates (ORR) were of 0 to 4.8%. Higher doses (10 mg/kg) provided longer median overall survival rates, but similar overall response rates compared to lower doses.	[170,171,172,173,174,175]
Pembrolizumab Nivolumab Ipilimumab	Retrospective cohort study Clinical trials (NCT02626962.P1)	Less effective in UM than cutaneous melanoma due to lower mutational burden. Checkpoint inhibitors show limited effectiveness in UM due to a lower number of neoantigens. Combined nivolumab and ipilimumab showed a median OS of 12.7 months. Systemic therapies showed a median OS of 9.3 months.	[176,177,178,179,180,181,182,183]
Tebentafusp	Previously untreated HLA-A*0201-positive patients with metastatic uveal melanoma	Demonstrated overall survival benefit in metastatic UM but limited to patients who are HLA-A*0201 positive.	[10]
Dual checkpoint inhibitors	Meta-analysis	Dual checkpoint inhibitors are more effective than single agents for metastatic UM.	[184]
Oncolytic viruses
T-VEC	In vitro UM cell lines Clinical trials (NCT02509507)	Showed potential with local control and durable systemic response. Alters tumor microenvironment to enhance immune attack.	[185,186]
ECHO-7 Coxsackieviruses HF-10	In vitro UM cell lines	These viruses are being explored for efficacy in UM, with promising results in initial studies.	[186,187]
HSV-EGFP VSV-IFNβ-TYRP1	In vitro UM cell lines Clinical trials	Demonstrated effectiveness in vitro and in vivo. VSV-IFNβ-TYRP1 is safe in patients with metastatic UM. Combination with checkpoint inhibitors enhances immune response in patients with metastatic UM (coxsackie (CAVATAK) combined with Ipilimumab).	[188,189,190]
Adoptive T Cell therapy
TIL therapy	TILs from primary UM NOD/SCID IL2 receptor gamma (NOG) knockout mouse strain	Induced significant tumor regression in a subset of patients, suggesting manipulation of tumor microenvironment can enhance anti-tumor responses. TILs show potential as an adjuvant treatment for UM with high metastatic risk. CAR-T cells effective in vitro and in vivo against UM cells and resistant tumors in specific mouse models.	[191,192,193]