Strong antigenic heterogeneity in solid tumors defined by neoepitopes may still allow to use the immunogenic cancer – testis antigen NY-ESO-1 if sufficiently expressed. Mesothelin CARs have shown to be associated with epitope spreading and induce T-cell responses against private antigens. Commonly shared TAAs may represent a cellular ‘first line’ treatment, enhancement possible with checkpoint inhibitors. This evidence concerns the gene MSLN and cancer.