Yutaro Kaneko1, Ryo Hatano2, Naoto Hirota3, Nicolas Isambert4, Véronique Trillet-Lenoir5, Benoit You5, Jérôme Alexandre6, Gérard Zalcman7, Fanny Valleix8, Thomas Podoll9, Yoshimi Umezawa3, Seiichi Takao3, Satoshi Iwata2, Osamu Hosono10, Tetsuo Taguchi11, Taketo Yamada12,13, Nam H Dang14, Kei Ohnuma2, Eric Angevin15, Chikao Morimoto2. 1. Y's AC Co., Ltd., 2-6-8, Kudan-minami, Chiyoda-ku, Tokyo, 102-0074, Japan. y.kaneko@ys-ac.com. 2. Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan. 3. Stella Co., Ltd., Tokyo, Japan. 4. Centre Georges-François Leclerc, Unité de Phases Précoces, Dijon, France. 5. Institut de Cancérologie des Hospices Civils de Lyon, CITOHL, Lyon, France. 6. Hôpital Cochin, Paris, France. 7. Centre Hospitalier Universitaire (CHU) de Caen, Centre de Recherche Clinique/Essais de phases précoces, Caen, France. 8. FV Clinical subcontractor for SynteractHCR SAS, Levallois-Perret, France. 9. Y's therapeutics Inc., Redwood City, CA, USA. 10. Department of Rheumatology and Allergy, IMSUT Hospital, The University of Tokyo, Tokyo, Japan. 11. Graduate School of Medicine, Osaka University, Osaka, Japan. 12. Saitama Medical University, Saitama, Japan. 13. Keio University School of Medicine, Tokyo, Japan. 14. Division of Hematology/Oncology, University of Florida, Gainesville, FL, USA. 15. Gustave Roussy, Drug Development Department (DITEP), Université Paris-Saclay, Villejuif, France.
Abstract
BACKGROUND: The phase I trial of the humanized anti-CD26 monoclonal antibody YS110 for CD26-expressing tumors was conducted recently. The present study identifies a potential prognostic biomarker for CD26-targeted therapy based on the phase I data. METHODS: Box and Whisker plot analysis, Scatter plot analysis, Peason product moment correlation/Spearman's rank-difference correlation, Bar graph analysis, and Receiver Operating Characteristics (ROC) were used to examine the correlation between sCD26 titer variation with YS110 administration and tumor volume change, RECIST criteria evaluation and progression free survival (PFS). Mechanism for serum sCD26 titer variation was confirmed by in vitro experimentation. RESULTS: Serum sCD26/DPP4 titer was reduced following YS110 administration and gradually recovered until the next infusion. Serum sCD26/DPP4 titer before the next infusion was sustained at lower levels in Stable Disease (SD) cases compared to Progressive Disease cases. ROC analysis defined the cut-off level of serum sCD26/DPP4 titer variation at day 29 pre/post for the clinical outcome of SD as tumor response or PFS. In vitro experimentation confirmed that YS110 addition reduced sCD26 production from CD26-expressing tumor and non-tumor cells. CONCLUSIONS: Our study indicates that serum sCD26/DPP4 titer variation in the early phase of YS110 treatment is a predictive biomarker for evaluating therapeutic efficacy.
BACKGROUND: The phase I trial of the humanized anti-CD26 monoclonal antibody YS110 for CD26-expressing tumors was conducted recently. The present study identifies a potential prognostic biomarker for CD26-targeted therapy based on the phase I data. METHODS: Box and Whisker plot analysis, Scatter plot analysis, Peason product moment correlation/Spearman's rank-difference correlation, Bar graph analysis, and Receiver Operating Characteristics (ROC) were used to examine the correlation between sCD26 titer variation with YS110 administration and tumor volume change, RECIST criteria evaluation and progression free survival (PFS). Mechanism for serum sCD26 titer variation was confirmed by in vitro experimentation. RESULTS: Serum sCD26/DPP4 titer was reduced following YS110 administration and gradually recovered until the next infusion. Serum sCD26/DPP4 titer before the next infusion was sustained at lower levels in Stable Disease (SD) cases compared to Progressive Disease cases. ROC analysis defined the cut-off level of serum sCD26/DPP4 titer variation at day 29 pre/post for the clinical outcome of SD as tumor response or PFS. In vitro experimentation confirmed that YS110 addition reduced sCD26 production from CD26-expressing tumor and non-tumor cells. CONCLUSIONS: Our study indicates that serum sCD26/DPP4 titer variation in the early phase of YS110 treatment is a predictive biomarker for evaluating therapeutic efficacy.
Authors: L Ho; U Aytac; L C Stephens; K Ohnuma; G B Mills; K S McKee; C Neumann; R LaPushin; F Cabanillas; J L Abbruzzese; C Morimoto; N H Dang Journal: Clin Cancer Res Date: 2001-07 Impact factor: 12.531
Authors: Virginia Boccardi; Luigi Marano; Rosaria Rita Amalia Rossetti; Maria Rosaria Rizzo; Natale di Martino; Giuseppe Paolisso Journal: BMC Cancer Date: 2015-10-15 Impact factor: 4.430
Authors: J Yamamoto; K Ohnuma; R Hatano; T Okamoto; E Komiya; H Yamazaki; S Iwata; N H Dang; K Aoe; T Kishimoto; T Yamada; C Morimoto Journal: Br J Cancer Date: 2014-04-17 Impact factor: 7.640