Uveal melanoma is a rare neoplasm with poor prognosis in the metastatic setting. 
Unlike cutaneous melanoma, treatment with kinase inhibitors or immune checkpoint 
inhibitors is not effective. Glycoprotein 100 (Gp-100) is a protein highly 
expressed in melanocytes and melanoma that has recently been effectively 
targeted by tebentafusp, a first-in-class bispecific protein of the 
immune-mobilizing monoclonal T cell receptors against cancer (ImmTACs) family. 
Tebentafusp targets tumor cells that express a peptide of Gp-100 presented by 
HLA*A0201, creating an immune synapse that kills targeted tumor cells. Recently, 
a randomized phase III trial reported an overall survival benefit for 
tebentafusp in patients with untreated metastatic uveal melanoma. The aim of 
this comprehensive review is to summarize evidence of Gp-100 as a therapeutic 
target in melanoma, and the preclinical and clinical development of tebentafusp 
as a novel therapeutic strategy for patients with uveal melanoma.