However, Quintarelli et al. demonstrated that OX40 incorporated into third-generation CARs, CD28.OX40.CD3ζ or 4-1BB.OX40.CD3ζ decreases INFγ and IL2 production and the anti-tumor activity when compared to a CAR construct including the combination of CD28.4-1BB.CD3ζ [67]. This evidence concerns the gene TNFRSF9 and neoplasm.