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Expression of activated integrin β7 in multiple myeloma patients

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Abstract

Multiple myeloma (MM) is still extremely difficult to cure, and new therapeutic drugs are needed. We recently found that integrin β7 is constitutively activated in MM cells, and chimeric antigen receptor (CAR) T cells targeting activated integrin β7 have a significant anti-MM effect. In this study, we performed flow cytometry analysis of the expression of activated integrin β7 in bone marrow cells from 137 symptomatic MM patients. In 60/137 (44%) MM patients, activated integrin β7 was detected in most MM cells (> 80% of MM cells were in the positive gate). Activated integrin β7 was highly expressed in MM cells even in heavily treated patients. It also showed high expression in many CD38lo/−CD138−CD19+B cells, which reportedly include clonotypic B cells, in the bone marrow of MM patients. Taken together, these results suggest that CAR T-cell therapy targeting activated integrin β7 has the potential to benefit many patients with relapsed or refractory MM.

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Acknowledgements

This study was funded by Otsuka Pharmaceutical.

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Osaka University Graduate School of Medicine, 2-2 Yamada-Oka, Suita, Osaka, 565-0871, Japan

    Naoki Hosen

  2. Department of Cellular Immunotherapy, Osaka University Immunology Frontier Research Center, Suita, Japan

    Naoki Hosen

  3. Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan

    Satoshi Yoshihara

  4. Department of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan

    Hiroyuki Takamatsu

  5. Department of Hematology and Oncology, Institute of Medical and Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

    Masaki Ri & Shinsuke Iida

  6. Division of Hematology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Yasuyuki Nagata

  7. Department of Hematology, Ogaki Municipal Hospital, Ogaki, Japan

    Hiroshi Kosugi

  8. Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan

    Yoshimitsu Shimomura

  9. Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan

    Ichiro Hanamura

  10. Department of Hematology, Osaka International Cancer Institute, Osaka, Japan

    Shigeo Fuji

  11. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Koichiro Minauchi

  12. Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Junya Kuroda

  13. Department of Hematology/Oncology, Tokai University School of Medicine, Tokyo, Japan

    Rikio Suzuki

  14. Department of Hematology Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

    Noriko Nishimura

  15. Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan

    Nobuhiko Uoshima

  16. Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Hirohisa Nakamae

  17. Department of Hematology, Rheumatology, and Infectious Diseases, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Yawara Kawano

  18. Department of Hematology, Hyogo Cancer Center, Akashi, Japan

    Ishikazu Mizuno & Hiroshi Gomyo

  19. Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan

    Kenshi Suzuki

  20. Department of Hematology, Tokushima Prefectural Central Hospital, Tokushima, Japan

    Shuji Ozaki

  21. Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Shingen Nakamura

  22. Department of Hematology/Oncology, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Yoichi Imai

  23. Department of Hematology, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    Masahiro Kizaki

  24. Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan

    Eiju Negoro

  25. Department of Hematology, Gunma University Graduate School of Medicine, Maebashi, Japan

    Hiroshi Handa

Authors
  1. Naoki Hosen
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  2. Satoshi Yoshihara
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  3. Hiroyuki Takamatsu
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  4. Masaki Ri
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  5. Yasuyuki Nagata
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  6. Hiroshi Kosugi
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  7. Yoshimitsu Shimomura
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  8. Ichiro Hanamura
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  9. Shigeo Fuji
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  10. Koichiro Minauchi
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  11. Junya Kuroda
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  12. Rikio Suzuki
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  13. Noriko Nishimura
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  14. Nobuhiko Uoshima
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  15. Hirohisa Nakamae
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  16. Yawara Kawano
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  17. Ishikazu Mizuno
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  18. Hiroshi Gomyo
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  19. Kenshi Suzuki
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  20. Shuji Ozaki
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  21. Shingen Nakamura
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  22. Yoichi Imai
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  23. Masahiro Kizaki
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  24. Eiju Negoro
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  25. Hiroshi Handa
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  26. Shinsuke Iida
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Corresponding author

Correspondence to Naoki Hosen.

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Conflict of interest

This study was supported by Otsuka Pharmaceutical Co., Ltd. NH, MR, JK and SI received research funding and honoraria from Otsuka Pharmaceutical Co., Ltd. All other authors do not have financial relationship with Otsuka Pharmaceutical Co., Ltd.

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Hosen, N., Yoshihara, S., Takamatsu, H. et al. Expression of activated integrin β7 in multiple myeloma patients. Int J Hematol 114, 3–7 (2021). https://doi.org/10.1007/s12185-021-03162-2

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  • DOI: https://doi.org/10.1007/s12185-021-03162-2

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