TY - JOUR
T1 - Anti-GPRC5D/CD3 bispecific T-cell-redirecting antibody for the treatment of multiple myeloma
AU - Kodama, Tatsushi
AU - Kochi, Yu
AU - Nakai, Waka
AU - Mizuno, Hideaki
AU - Baba, Takeshi
AU - Habu, Kiyoshi
AU - Sawada, Noriaki
AU - Tsunoda, Hiroyuki
AU - Shima, Takahiro
AU - Miyawaki, Kohta
AU - Kikushige, Yoshikane
AU - Mori, Yasuo
AU - Miyamoto, Toshihiro
AU - Maeda, Takahiro
AU - Akashi, Koichi
N1 - Funding Information:
We thank N. Ikeda, N. Kimura, I. Matsuo, K. Kuramoto, S. Kuramoto, and M. Muraoka for the biological assay and the in vivo study. We also thank Ishida Ladies Clinic for providing cord blood samples. This work was supported, in part, by a Grant-in-Aid for Scientific Research on Innovative Areas (grant no.
Funding Information:
Y. Kochi reports receiving a commercial research grant from Chugai Pharmaceutical Co. Ltd. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
We thank N. Ikeda, N. Kimura, I. Matsuo, K. Kuramoto, S. Kuramoto, and M. Muraoka for the biological assay and the in vivo study. We also thank Ishida Ladies Clinic for providing cord blood samples. This work was supported, in part, by a Grant-in-Aid for Scientific Research on Innovative Areas (grant no. 22130001 and 22130002, to K. Akashi), a Grant-in-Aid for Challenging Exploratory Research (grant no. 24659463 and 15K15365, to K. Akashi), a Grant-in-Aid for Scientific Research (A; grant no. 25253069 and 16H02662, to K. Akashi), a Grant-in-Aid for Young Scientists (A; grant no. 26713034 and 16H06250, to Y. Kikushige), a Grant-in-Aid for Scientific Research (B; grant no. 23390254, to T. Miyamoto), Japan Agency for Medical Research and Development (AMED) grants (JP17ck0106163h0002 and JP17cm0106507h0002), Grant-in-Aid for Scientific Research S (16H06391), Grant-in-Aid for Scientific Research A (17H01567, to T. Maeda), a Grant-in-Aid for Young Scientists (16K19578, to K. Miyawaki), and a Grant-in-Aid for Scientific Research on Innovative Areas (grant no. 25115002 and 16H05340, to T. Miyamoto). This work was also supported, in part, by a contribution from Social Medical
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019
Y1 - 2019
N2 - Although treatment advances over recent decades have significantly improved survival of patients with multiple myeloma, there is still an unmet medical need for more effective treatments. In this study, we identified G-protein-coupled receptor family C group 5 member D (GPRC5D) expression on the surface of malignant cells involved in multiple myeloma, but except for plasma cells and B cells, not at appreciable levels on normal hematopoietic cells and bone marrow progenitors, including hematopoietic stem cells. In addition, we constructed IgG-based anti-GPRC5D/CD3 bispecific T-cell-redirecting antibodies (GPRC5D TRAB), which suppressed the tumor growth of GPRC5D-positive myeloma cells through the activation of T cells in vitro and in vivo in xenograft models. Collectively, these findings suggest that GPRC5D is an antigen specific to multiple myeloma and a potential target of TRAB therapy.
AB - Although treatment advances over recent decades have significantly improved survival of patients with multiple myeloma, there is still an unmet medical need for more effective treatments. In this study, we identified G-protein-coupled receptor family C group 5 member D (GPRC5D) expression on the surface of malignant cells involved in multiple myeloma, but except for plasma cells and B cells, not at appreciable levels on normal hematopoietic cells and bone marrow progenitors, including hematopoietic stem cells. In addition, we constructed IgG-based anti-GPRC5D/CD3 bispecific T-cell-redirecting antibodies (GPRC5D TRAB), which suppressed the tumor growth of GPRC5D-positive myeloma cells through the activation of T cells in vitro and in vivo in xenograft models. Collectively, these findings suggest that GPRC5D is an antigen specific to multiple myeloma and a potential target of TRAB therapy.
UR - http://www.scopus.com/inward/record.url?scp=85071785136&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071785136&partnerID=8YFLogxK
U2 - 10.1158/1535-7163.MCT-18-1216
DO - 10.1158/1535-7163.MCT-18-1216
M3 - Article
C2 - 31270154
AN - SCOPUS:85071785136
SN - 1535-7163
VL - 18
SP - 1555
EP - 1564
JO - Molecular cancer therapeutics
JF - Molecular cancer therapeutics
IS - 9
ER -
