Gp-100 as a Novel Therapeutic Target in Uveal Melanoma

• Published in: Cancers Vol. 13; no. 23; p. 5968
• Main Authors: Martinez-Perez, Daniel, Viñal, David, Solares, Isabel, Espinosa, Enrique, Feliu, Jaime
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 27-11-2021; MDPI
• Subjects: African Americans; Antigens; Cancer therapies; Chemical bonds; Chemotherapy; Clinical trials; Cytokines; Dendritic cells; FDA approval; Glycoproteins; Histocompatibility antigen HLA; Immune checkpoint inhibitors; Immunotherapy; Lymphocytes; Lymphocytes T; Medical prognosis; Melanocytes; Melanoma; Metastases; Metastasis; Neoplasia; Oncology; Patients; Peptides; Proteins; Review; T cell receptors; Therapeutic applications; Tumor cells; Vaccines
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers13235968

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.