Computational analysis of TYRP1+ CAR T-cells targeting CD19+ and CD28+ melanoma cells

Melanoma is a type of skin cancer originating in the melanocytes and is recognized as one of the most severe and challenging forms of skin cancer to treat. Tyrosinase-related protein 1 (TYRP1) is a crucial protein involved in melanin production and is notably overexpressed in melanoma cells. Recently, TYRP1 has been identified as a prospective target in CAR T-Cell therapy, particularly for CD28 receptor binding, to treat patients with rare and cutaneous melanoma subtypes. We hypothesize that the receptor binds to a specific orientation to form a strong interaction. This study aims to elucidate the binding mechanism between CD28+ CAR-T cells and TYRP1-expressing melanoma cells to aid in developing novel therapeutics against melanoma. Initially, molecular docking simulations of CD28 and TYRP1 receptors were conducted. Subsequently, YASARA software was used to perform molecular dynamics simulations of the CD28-TYRP1 complex. The computational analysis revealed strong and stable hook-like interactions between the two receptors, formed at druggable sites as suggested by the P2Rank web server. This investigation into T cell receptor interactions will significantly enhance CAR-T cell therapy's effectiveness for treating cutaneous and rare melanoma subtypes.