Chimeric antigen receptor (CAR) T-cell therapy targeting the surface protein TYRP1 may be effective in patients with rare subtypes of melanoma whose disease does not respond to treatment with immune checkpoint inhibitors, according to a recent study published by Jilani et al in Nature Communications. Researchers used three melanoma datasets to identify TYRP1 as an antigen expressed at higher levels in tumor cells than in normal cells. They explained that although TYRP1 proteins are most commonly found inside the cells of melanosomes, some of them are transported to the surface of melanoma cells. Further, about 30%, 60%, and 90% of patients with cutaneous, acral and mucosal, and uveal melanoma tumors, respectively, present with TYRP1 overexpression. The researchers developed a novel CAR T-cell therapy capable of detecting the TYRP1 surface protein in melanoma cells with TYRP1 overexpression. After conducting in vitro and in vivo murine models and patient-derived cutaneous, acral, and uveal melanoma models, the researchers observed significant antitumor activity with the novel therapy, and no systemic or off-tumor severe toxicities. The researchers hope to further analyze the novel CAR T-cell therapy in a phase I clinical trial. In a companion press release on the findings from UCLA Health, the study authors concluded: “If proven safe and effective in human trials, this treatment presents an exciting prospect for future advancements in the fight against cancer.”
March 06, 2024