Development of antibody therapy targeting multiple myeloma-specific glyco-epitope

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461404
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: Hosen Naoki 大阪大学, 医学系研究科, 寄附講座准教授 (10456923)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 多発性骨髄腫

Outline of Final Research Achievements

In this study, we discovered that an antigen formed in CD98 heavy chain (hc) protein in cells undergoing endoplasmic reticulum (ER) stress could exert as a specific target for mAb therapy against multiple myeloma (MM). We first identified R8H283 as a mAb that specifically bound to MM cells after screening more than 10,000 anti-MM mAb clones. Although R8H283 specifically recognized CD98hc, which is expressed on most normal hematioietic cells, R8H283 binding to normal hematopoietic cells was not detected. After induction of endoplasmic reticulum (ER) stress, which is observed in most MM cells, by tunicamycin or thapsigargin, R8H283-negative hematopoietic cells expressed low molecular weight CD98hc and gained R8H283 reactivity. These results suggest that R8H283 reacted with CD98hc protein with altered modification under ER stress. Furthermore, R8H283 exhibited striking anti-MM effects in vitro and in vivo without damaging normal hematopoietic cells.

Free Research Field

血液内科学