In addition, simultaneous agonism of co-stimulatory pathways and antagonism of inhibitory checkpoints allows one to “step on the gas while taking the foot off the brakes.” In solid tumor models, combined treatment with agonistic anti-OX40 mAb and anti-CTLA-4 mAb improved survival and induced tumor regression through expansion of effector CD8 T-cells [85]. This evidence concerns the gene TNFRSF4 and neoplasm.