Our group first demonstrated in 2001 that human blood T cells can fully be activated by a CD28-ζ CAR independently of CD80/CD86 on cancer cells indicating CAR-autonomous signaling through both CD3ζ and CD28.69,70 The demonstrated full CAR-driven activation of primary blood T cells was a crucial step toward clinical application; T cell hybridoma or leukemic cells used before are not adequate in this respect due to their neoplastic transformation. Here, CD28 is linked to cancer.