Josep Maria M. Piulats, MD, PhD, CRI CLIP Investigator Fundacio Institut D'Investigacio Biomedica de Bellvitge, L'Hospitalet del Llobregat Area of Research: Melanoma Dr. Piulats’s project is focused on the development of a new cellular therapy against uveal melanoma (UM). Uveal melanoma (UM) is the most common and deadly ocular malignancy in adults with approximately 50% of patients becoming metastatic. Until recently, the median overall survival (OS) was less than 12 months. Two immunotherapies based on tumor infiltrating cells (TILs) infusion or Tebentafusp, a molecule recognizing the antigen gp100, have shown an improvement in OS. Regrettably, Tebentafusp can only be used in 40% of patients expressing a particular haplotype and must be administered for the rest of their lives. TILs infusion is an expensive, toxic, and long procedure that requires removal of a metastatic lesion and more than a month of TIL manufacturing, thus limiting the patients that can benefit from this therapy. Dr. Piulats has found memory T cells from peripheral blood recognizing the mutated epitopes of the two typical driver mutations of UM GNAQ and GNA11, in patients with UM. Dr. Piulats aims to characterize the reactive T cell receptors (TCR) against these epitopes, the associated haplotype and minimal peptide bound to them to develop a novel cellular therapy product that would present several advantages: (1) It targets the driver mutation associated to UM, avoiding to some extent resistance mechanisms and being specific for tumor cells (2) it is an off-the- shelf product useful for all patients sharing the same haplotype that stands to reduce the overall cost and shorten the time to treatment to 2 weeks; (3) it is a single dose therapy, and (4) it can be combined with other therapies to increase efficacy. Projects and Grants Generation of personalized TCR therapy against GNAQ/11 Q209L mutations in Uveal melanoma Fundacio Institut D’Investigacio Biomedica de Bellvitge, L’Hospitalet del Llobregat | Melanoma | 2023
