Abstract：
:Cancer-specific cell-surface antigens are ideal targets for monoclonal antibody (mAb)-based immunotherapy but are likely to have previously been identified in transcriptome or proteome analyses. Here, we show that the active conformer of an integrin can serve as a specific therapeutic target for multiple myeloma (MM). We screened >10,000 anti-MM mAb clones and identified MMG49 as an MM-specific mAb specifically recognizing a subset of integrin β7 molecules. The MMG49 epitope, in the N-terminal region of the β7 chain, is predicted to be inaccessible in the resting integrin conformer but exposed in the active conformation. Elevated expression and constitutive activation of integrin β7 conferred high MMG49 reactivity on MM cells, whereas MMG49 binding was scarcely detectable in other cell types including normal integrin β7+ lymphocytes. T cells transduced with MMG49-derived chimeric antigen receptor (CAR) exerted anti-MM effects without damaging normal hematopoietic cells. Thus, MMG49 CAR T cell therapy is promising for MM, and a receptor protein with a rare but physiologically relevant conformation can serve as a cancer immunotherapy target.
journal_name
Nat Medjournal_title
Nature medicineauthors
Hosen N,Matsunaga Y,Hasegawa K,Matsuno H,Nakamura Y,Makita M,Watanabe K,Yoshida M,Satoh K,Morimoto S,Fujiki F,Nakajima H,Nakata J,Nishida S,Tsuboi A,Oka Y,Manabe M,Ichihara H,Aoyama Y,Mugitani A,Nakao T,Hino M,doi
10.1038/nm.4431subject
Has Abstractpub_date
2017-12-01 00:00:00pages
1436-1443issue
12eissn
1078-8956issn
1546-170Xpii
nm.4431journal_volume
23pub_type
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