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.

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We thank the Kinki Cord Blood Bank for CB samples and T. Yamane (Osaka City General Hospital) and K. Koh (Osaka General Hospital for West Japan Railway Company) for MM samples. We also thank K. Terasaki, S. Ikeda, Y. Hayami, R. Inada, R. Urakawa, S. Hashiguchi, M. Iwai, and A. Kosugi for technical assistance, and Y. Kanakura (Osaka University), R. Burger (University of Kiel), I. Weissman (Stanford University), T. Kitamura (Tokyo University), and the NIH AIDS Reagents program for providing materials. This work was supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas (Analysis and Synthesis of Multidimensional Immune Organ Network) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to J.T.); the Project for Development of Innovative Research on Cancer Therapeutics and Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development AMED (to N.H.); JSPS KAKENHI grant JP26461404 (to N.H.); and Japan Agency for Medical Research and Development–Core Research for Evolutional Science and Technology grant 15652237 (to A.K.).

Author information

Author notes

    • Yukiko Matsunaga

    Present address: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

    • Yukiko Matsunaga
    •  & Kana Hasegawa

    These authors contributed equally to this work.


  1. Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.

    • Naoki Hosen
    • , Kana Hasegawa
    • , Yuki Nakamura
    • , Mio Makita
    • , Kouki Watanabe
    • , Mikako Yoshida
    • , Kei Satoh
    •  & Yoshihiro Oka
  2. Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.

    • Naoki Hosen
    • , Sumiyuki Nishida
    • , Yoshihiro Oka
    •  & Atsushi Kumanogoh
  3. WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.

    • Naoki Hosen
    • , Yoshihiro Oka
    • , Kiyoshi Takeda
    •  & Atsushi Kumanogoh
  4. Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.

    • Yukiko Matsunaga
    •  & Junichi Takagi
  5. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

    • Hiroshi Matsuno
    •  & Junichi Nishimura
  6. Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.

    • Soyoko Morimoto
    • , Jun Nakata
    •  & Akihiro Tsuboi
  7. Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.

    • Fumihiro Fujiki
    • , Hiroko Nakajima
    •  & Haruo Sugiyama
  8. Department of Hematology, Osaka General Hospital of West Japan Railway Company, Osaka, Japan.

    • Masahiro Manabe
  9. Department of Hematology, Fuchu Hospital, Osaka, Japan.

    • Hiroyoshi Ichihara
    • , Yasutaka Aoyama
    •  & Atsuko Mugitani
  10. Department of Hematology, Osaka City General Hospital, Osaka, Japan.

    • Takafumi Nakao
  11. Department of Hematology and Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.

    • Masayuki Hino
  12. Division of Immuno-Gene & Cell Therapy (Takara Bio), Jichi Medical University, Tochigi, Japan.

    • Ryosuke Uchibori
    •  & Keiya Ozawa
  13. Institute of Medical Science, University of Tokyo, Tokyo, Japan.

    • Keiya Ozawa
  14. Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.

    • Yoshihiro Baba
  15. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

    • Seitaro Terakura
  16. Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan.

    • Naoki Wada
    •  & Eiichi Morii
  17. Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.

    • Kiyoshi Takeda
  18. Japan Agency for Medical Research and Development–Core Research for Evolutional Science and Technology (AMED-CREST), Japan.

    • Kiyoshi Takeda
    •  & Atsushi Kumanogoh
  19. Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.

    • Yusuke Oji


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N.H. and J.T. designed the experiments; N.H., Y.M., K.H., H.M., Y.N., M. Makita., K.W., M.Y., K.S., S.M., F.F., H.N., J.Nakata., S.N., A.T., Y.Oka., R.U., K.O., Y.B., S.T., N.W., E.M., J.Nishimura., and Y.Oji. performed the experiments; M.Manabe., H.I., Y.A., A.M., T.N., and M.H. collected and analyzed clinical samples; N.H., Y.M., K.H., and J.T. analyzed the data; N.H., Y.M., K.H., K.T., H.S., J.T., and A.K. wrote the manuscript; and all authors reviewed and approved the final version of the manuscript.

Competing interests

N.H., H.S., J.T., and A.K. have applied for a Japanese patent entitled 'Antibody' through the Osaka University Office for University-Industry Collaboration. The other authors declare no competing financial interests.

Corresponding author

Correspondence to Naoki Hosen.

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