Recently, Wu et al. described the application of a novel trispecific antibody format, termed a crossover dual variable (CODV) format, to simultaneously target CD38, CD3, and CD28 for treating multiple CD38-positive hematological malignancies, such as MM, AML, and chronic lymphocytic leukemia.135 Dual engagement of CD3 and CD28, representing the first and second signals required for optimal T cell proliferation, respectively, afforded efficient T cell activation and costimulation and boosted sustained T cell proliferation to kill CD38-positive MM cells in vitro and in vivo.135. The gene discussed is CD28; the disease is B-cell chronic lymphocytic leukemia.