Mouse melanomas treated with epitope-standardized adoptive T cell therapy targeting endogenously encoded melanosomal RAB38

Using a CRISPR-Cas9 based approach we fused a model CD8 T-cell epitope to the C-termini of endogenous gene products. By this approach we could target different endogenous gene products with the same epitope-specific T cell receptor (TCR)-transgenic CD8+ T-cells. This epitope-standardized adoptive T-cell therapy (esACT) allowed us to directly compare how function and regulation of epitope-encoding gene products influence responsiveness and mechanisms of immune evasion. Here, we targeted the melanosomal protein RAB38 and analyzed non-treated and esACT-recurrent melanomas in syngeneic mice. Our approach revealed a diversity genetic and non-genetic of immune evasion mechanisms in melanoma in part dependent on the targeted gene product.