Now in their third generation, CARs are hybrid receptors formed by the fusion of an extracellular tumor-specific antibody fragment, a CD3-derived ITAM signaling chain, and a co-stimulatory signaling domain.43,44 The CARs have been explored with some success against CD19 in B-cell acute lymphoblastic leukemia (B-ALL),45 carbonic anhydrase in renal cell carcinoma,46 and L1 adhesion molecule (CD171) in neuroblastoma,47 among other antigens (reviewed by Kershaw et al.35). The gene discussed is L1CAM; the disease is precursor B-cell acute lymphoblastic leukemia.