| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| 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.
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