Interestingly, strategies have been designed to enhance CAR T-cell therapy efficiency, such as reducing tumor bulk before adoptive cell therapy, optimizing the Th2-to-Th1 ratio of infused CAR T-cells, pre-conditioning to deplete Tregs (by inhibiting CTLA4, CD-25 targeting, TNFα agonism or combining with rosiglitazone), increasing CD8+ TILS (with metformin or by inhibiting TGF-β), increasing macrophage activation (by targeting CSF1, CCR2 or Bruton tyrosine kinase (BTK)) and even co-expressing albumin on the surface of CAR T-cells (to enhance accumulation in the tumor) [134]. Here, TNF is linked to neoplasm.