Since the use of anti-CD4 mAbs showed a reversible depletion of CD4+ cells in T-cell lymphoma patients without inducing immunosuppression [77–79], third-generation anti-CD4 CARs (containing 4-1BB and CD28 costimulatory domains) were then developed, demonstrating in vitro and in vivo preclinical efficacy [73, 80]. The gene discussed is CD28; the disease is T-cell non-Hodgkin lymphoma.