CD28 and neoplasm: Adoptive cell therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has shown great potency as one of the most effective cancer immunotherapies.1, 2, 3 CARs are synthetic receptors consisting of an extracellular domain, a hinge region, a transmembrane domain, and intracellular signal domains (e.g., CD3-zeta, CD28, and 41BB) that initiate T cell activation.4, 5, 6 CARs can promote non-major histocompatibility complex (MHC)-restricted recognition of cell surface components, bind tumor antigens directly, and trigger a T cell anti-tumor response.7