Similarly, approaches to modify PD1 signaling using overexpression of a dominant-negative PD-1 receptor (55), chimeric PD-1 fused to the intracellular signaling domain of CD28 (56), shRNA-mediated knockdown (55) or CRISPR/Cas9-mediated knockout of PD-1 on adoptively transferred T-cells (57) has led to improved tumor recognition and clearance in murine models. The gene discussed is CD28; the disease is neoplasm.