In a CLL setting, this could also function as an indirect mechanism to enhance the native immune response and may activate CLL cells to upregulate costimulatory molecules in vivo. Combining cellular therapies with small molecules that enhance either CAR T-cell or CLL activation such as lenalidomide (40–42, 80–82) or CD40 agonists (78, 83) may improve therapeutic responses in CLL. This evidence concerns the gene CD40 and B-cell chronic lymphocytic leukemia.