Besides, engineering co-stimulatory signals is proposed to prolong T cell persistence and enhance anti-tumor activity, which can be achieved by coupling T cell activating signals (CD3ζ) with co-stimulating signals (CD28, OX40, 4-1BB), or using chimeric switch receptors which link exodomain of CTLA-4, PD-1 or TIGHT to intradomain of CD28 [90–95]. The gene discussed is CD28; the disease is neoplasm.