In particular, first generation CARs failed because of poor T cell expansion and adverse effects; new second and third generation CARs have solved at least in part these problems and good pre-clinical in vivo results, i.e. tumor regression, longer persistence in circulation and better localization towards the tumor, have been obtained with MOv19-based CAR constructs containing the co-stimulatory motif of CD137 or CD27 [118, 135]. Here, TNFRSF9 is linked to neoplasm.