The development of novel treatment strategies for ATL patients by mogamulizumab

2015 Fiscal Year Final Research Report

• Project/Area Number: 25290058
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Nagoya City University
• Principal Investigator: ISHIDA TAKASHI 名古屋市立大学, 医学(系)研究科(研究院), 准教授 (80405183)
• Co-Investigator(Kenkyū-buntansha): UEDA Ryuzo 愛知医科大学, 医学部, 教授 (20142169)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: CCR4 / 制御性T細胞 / 成人T細胞白血病/リンパ腫 / 制御性T細胞 / IDO / mogamulizumab

Outline of Final Research Achievements

The multicenter prospective clinical observational study (MIMOGA study, UMIN000008696) is currently ongoing (as of April 2016). The interim analysis of 49 patients enrolled in this study demonstrated that skin-related AEs of grades 2-4 were observed in 7 patients (14.3%), but they had a trend towards prolonged OS (median OS, not reached vs 13.2 months), relative to patients with no or grade 1-2 skin-related AEs.　The analysis also demonstrated that ATL cells of effector Treg phenotype (CD45RA-FOXP3high, n=17) had a prolonged OS compared to the others (n=27) (median OS, not reached vs 12.8 months).
ATL cells and/or cells of the tumor microenvironment are likely to produce IDO, which would lead to a high Kyn/Trp ratio and a high Kyn level not only in the tumor microenvironment, but also in the blood. A high serum Kyn/Trp ratio was an independent significant detrimental prognostic factors in ATL patients. IDO is an attractive target for novel anti-ATL agents, combined with mogamulizumab.

Free Research Field

血液・腫瘍内科