TY - JOUR
T1 - CD26 is a potential therapeutic target by humanized monoclonal antibody for the treatment of multiple myeloma
AU - Nishida, Hiroko
AU - Hayashi, Mutsumi
AU - Morimoto, Chikao
AU - Sakamoto, Michiie
AU - Yamada, Taketo
N1 - Funding Information:
We thank Hiroshi Suzuki and Minako Suzuki at Department of Pathology, Keio University, School of Medicine and Akira Sonoda at Core Instrumentation Facility, Keio University, School of Medicine for their technical assistance and excellent advice. This work was supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (C) (16K07180 and 25430157) to H.N., (B) (26293081) to M. S., and (B) (16H04714 and 23390086) to T.Y., a Grant-in-Aid for Drug Design Biomarker Research from the Ministry of Health, Labor and Welfare of Japan (H24-B10-003) to C.M. and T.Y., and a Grant-in-Aid for Industrial Accident Clinical Research (H27-150401-01) from the Ministry of Health, Labor and Welfare of Japan to C.M. and T.Y. and the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation of Japan (07-17) to C.M. and T.Y.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/11/1
Y1 - 2018/11/1
N2 - CD26, a 110-kDa transmembrane glycoprotein that is expressed on several tumor cells including malignant lymphoma, has been implicated in tumorigenesis: however, little is known regarding its role in multiple myeloma (MM). Recently, we identified CD26 expression on human osteoclasts (OCs) and demonstrated that humanized IgG1 monoclonal antibody targeting CD26, huCD26mAb, inhibits human OC differentiation. Herein, we show that CD26 expression was present on plasma cells in the bone marrow tissues of MM patients. In vitro immunostaining studies revealed that although CD26 expression was low or absent on MM cell lines cultured alone, it was intensely and uniformly expressed on MM cell lines co-cultured with OCs. The augmented CD26 expression in MM cells was exploited to enhance anti-MM efficacy of huCD26mAb via a substantial increase in antibody-dependent cytotoxicity (ADCC) but not complement-dependent cytotoxicity (CDC). Moreover, huCD26mAb in combination with novel agents synergistically enhanced huCD26mAb induced ADCC activity against CD26+ MM cells compared with each agent alone. huCD26mAb additionally reduced the ratio of the side population (SP) fraction in CD26+ MM cells by ADCC. Finally, huCD26mAb significantly reduced the MM tumor burden and OC formation in vivo. These results suggest that CD26 is a potential target molecule in MM and that huCD26mAb could act as a therapeutic agent.
AB - CD26, a 110-kDa transmembrane glycoprotein that is expressed on several tumor cells including malignant lymphoma, has been implicated in tumorigenesis: however, little is known regarding its role in multiple myeloma (MM). Recently, we identified CD26 expression on human osteoclasts (OCs) and demonstrated that humanized IgG1 monoclonal antibody targeting CD26, huCD26mAb, inhibits human OC differentiation. Herein, we show that CD26 expression was present on plasma cells in the bone marrow tissues of MM patients. In vitro immunostaining studies revealed that although CD26 expression was low or absent on MM cell lines cultured alone, it was intensely and uniformly expressed on MM cell lines co-cultured with OCs. The augmented CD26 expression in MM cells was exploited to enhance anti-MM efficacy of huCD26mAb via a substantial increase in antibody-dependent cytotoxicity (ADCC) but not complement-dependent cytotoxicity (CDC). Moreover, huCD26mAb in combination with novel agents synergistically enhanced huCD26mAb induced ADCC activity against CD26+ MM cells compared with each agent alone. huCD26mAb additionally reduced the ratio of the side population (SP) fraction in CD26+ MM cells by ADCC. Finally, huCD26mAb significantly reduced the MM tumor burden and OC formation in vivo. These results suggest that CD26 is a potential target molecule in MM and that huCD26mAb could act as a therapeutic agent.
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U2 - 10.1038/s41408-018-0127-y
DO - 10.1038/s41408-018-0127-y
M3 - Article
C2 - 30348967
AN - SCOPUS:85055199680
SN - 2044-5385
VL - 8
JO - Blood cancer journal
JF - Blood cancer journal
IS - 11
M1 - 99
ER -