Abstract
Metastatic disease from uveal melanoma occurs in almost 50% of patients suffering from this ocular tumour, with median survival from development of symptoms being around 1 year. In contrast to cutaneous melanoma, kinase inhibitors and immune checkpoint inhibitors are usually ineffective in patients with metastatic uveal melanoma. Tebentafusp is a novel form of immunotherapy based on the immune-mobilising monoclonal T cell receptor against cancer (ImmTAC) platform, which comprises a soluble T cell receptor that is fused to an anti-CD3 single-chain variable fragment. The T cell receptor domain of tebentafusp targets cells present a human leukocyte antigen-A*02:01 complexed with a peptide derived from the melanoma-associated antigen gp100, which is expressed strongly by melanoma cells, weakly by normal melanocytes and minimally by other tissues. The anti-CD3 domain recruits CD3+ T cells (and, indirectly, other immune cells), redirecting these to the melanoma cells. The most common adverse events with tebentafusp are manageable and usually transient. Early survival data in patients with metastatic uveal melanoma are promising when considered alongside historical data. Based on these encouraging results, a randomised study comparing tebentafusp to investigator’s choice of therapy in metastatic uveal melanoma is ongoing.
Highlights
Almost 50% of patients with uveal melanoma (UM) develop metastatic disease (i.e., metastatic uveal melanoma), despite successful treatment of the primary ocular tumour [1]
We describe UM, cancer immunotherapy and the research that has translated tebentafusp from the laboratory to clinical trials
The Collaborative Ocular Melanoma Study reported no survival differences between patients treated with radiotherapy and those treated with enucleation [22]; it is not yet known whether metastasis occurs because of tumour recurrence after eye-conserving therapy [15,23]
Summary
Almost 50% of patients with uveal melanoma (UM) develop metastatic disease (i.e., metastatic uveal melanoma (mUM)), despite successful treatment of the primary ocular tumour [1]. Metastatic disease usually involves the liver and is commonly fatal within a year of the onset of symptoms [2]. Systemic therapy for metastases rarely prolongs life [3]; recent clinical trials have shown encouraging results with tebentafusp (formerly IMCgp100), a first-in-class, bispecific, fusion protein that redirects CD3+ T cells to gp100-expressing melanoma cells, inducing cytolysis [4,5]. We describe UM, cancer immunotherapy and the research that has translated tebentafusp from the laboratory to clinical trials
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