MAb therapy for advanced CTCL has been proposed [3] and numerous trials with alemtuzumab (anti-CD52) have shown modest to moderate clinical effects [35, 36, 37] . A recent trial with low dose alemtuzumab has shown complete remission in 50% of patients with refractory leukemic forms of the disease and without infectious disease complications although it was found completely ineffective in the treatment of MF [6] . A mAb to CD4 (GenMab) has been designated an orphan drug for the treatment of MF by the FDA [38] . While both approaches are designed to eliminate CTCL cells, there can be significant adverse effects from either treatment. CD52 is expressed by virtually all T and B cells, and the elimination of all CD4-positive cells has well-known negative consequences [39] . Clonal malignant T cells in these CTCL patients express uniformly high levels of CCR4, but variable to low levels of other skin homing addressins, including CLA, CCR10 and CCR6. CCR7, which is also uniformly highly expressed on leukemic variants of CTCL with T CM phenotype, is not expressed on the phenotypic T EM cells that are found in MF skin lesions [7] . Thus, only CCR4 is uniformly expressed on all forms of CTCL and has a restricted expression pattern on normal T cells, including Tregs [40] . Indeed, a subset of malignant T cells in some CTCL have been shown to act as CCR4 + Tregs to suppress antitumor responses and may fuel disease progression [41] . A therapeutic mAb that could preferentially target all forms of the disease and reverse Treg mediated immune suppression would be a major advance in the effective therapy of CTCL. The activity of mAb1567 in abrogating Treg mediated suppression of T effector cell function is described elsewhere (DK. Chang et al., in press). MAb KM0761, is another humanized anti-CCR4 mAb that has shown promising results in CTCL animal studies [42] and in clinical trials for refractory Adult T-cell leukemia (ATLL) and peripheral T cell lymphoma (PLCL) where good clinical activity without severe adverse side effects was seen [43, 44] . Our data support further exploration of the clinical potential of therapeutic mAbs that target CCR4 in CTCL.