Selecting uveal melanoma for PRAME‐TCR T cell immunotherapy

Abstract

PurposeTo determine which uveal melanoma may be candidates for PRAME‐directed immunotherapy using TCR‐modified autologous T cells.MethodsExpression of PRAME was determined in uveal melanoma by an Illumina array. HLA polymorphisms were determined on peripheral blood leukocytes. Clinical and histological characteristics of UM were derived from clinical charts and pathology reports.ResultsPRAME expression was highly variable; tumor size, thickness, and the presence of an inflammatory phenotype were associated with PRAME expression. 20/37 monosomy 3 cases expressed PRAME, and 8/20 disomy 3 tumors. 10‐year survival data on 60 UM showed worse survival of UM with high PRAME compared to those with a low PRAME. However, six of the eight PRAME‐positive disomy 3 cases died from metastases. With this information, all cases with PRAME‐positive primary tumors who carry the HLA‐A2 antigen should be followed closely for the development of metastases, as they can be candidates for PRAME‐TCR autologous T cell therapy.ConclusionsUveal melanoma may be good candidates for treatment with autologous T cells that have been modified so that they carry PRAME‐specific T cell receptors. Large uveal melanoma with a high PRAME expression (independent of chromosome 3 status) in HLA‐A2 positive patients are potential candidates for PRAME‐TCR autologous T cell therapy. A high PRAME expression, also in disomy 3 tumors, was associated with an inflammatory phenotype and with death due to metastases.