In this work we demonstrated: (1) that TRAIL-expressing 293T cells release TRAIL carried by EVs (EV-T), (2) that EV-T is highly efficient for selective apoptosis induction in cancer cells, (3) that CDK inhibition by dinaciclib drastically sensitizes TRAIL response in cancer cells, (4) that combination therapy with EV-T and dinaciclib led to complete eradication of subcutaneous A549 xenograft tumor growth without any adverse events observed. This evidence concerns the gene TNFSF10 and neoplasm.