Discussion
cancer, peripheral T-cell lymphoma
NON-SMALL CELL LUNG CANCER, PERIPHERAL T-CELL LYMPHOMA, HTLV-1-ASSOCIATED MYELOPATHY-TROPICAL SPASTIC PARAPARESIS, CANCER, SOLID TUMORS, ADULT T-CELL LEUKEMIA/LYMPHOMA
We conducted phase Ia and Ib clinical trials on KW-0761 to examine the selective depletion of Tregs in 49 patients with CCR4-negative solid cancer [Strategies targeting Tregs to increase anti-tumor immunity, including antibodies against CTLA-4, OX40, 4-1BB, and ICOS, have attracted attention [Treg reductions by KW-0761 have been analyzed in trials on adult T-cell leukemia/lymphoma, primary peripheral T-cell lymphoma, and HTLV-1-associated myelopathy-tropical spastic paraparesis, in which a wide range of dosages (0.003–1.0 mg/kg) of KW-0761 were examined [CT antigens, such as NY-ESO-1 and XAGE1, are known to show unique expression patterns and induce spontaneous humoral and cellular immune responses in various cancer patients [Regarding predictive markers of treatment efficacy, our group previously reported that serum NY-ESO-1 and XAGE1 antibody responses predicted good clinical responses with an anti-PD-1 treatment for non-small cell lung cancer [In conclusion, 49 patients were enrolled in the KW-0761 phase I trial, in which KW-0761 was safely administered and eTregs in peripheral blood were depleted in most patients. A durable clinical response was observed in some patients, and high lymphocyte levels before treatment may be a biomarker for the efficacy of the KW-0761 treatment. A phase I clinical trial on preoperative combination therapy of KW-0761 plus an anti-PD-1 treatment in patients with advanced or recurrent solid tumors is currently underway. The synergistic effect of KW-0761 for depleting Tregs and other immunotherapies is expected in the future.