Anti-GPRC5D/CD3 bispecific T-cell-redirecting antibody for the treatment of multiple myeloma

Tatsushi Kodama, Yu Kochi, Waka Nakai, Hideaki Mizuno, Takeshi Baba, Kiyoshi Habu, Noriaki Sawada, Hiroyuki Tsunoda, Takahiro Shima, Kohta Miyawaki, Yoshikane Kikushige, Yasuo Mori, Toshihiro Miyamoto, Takahiro Maeda, Koichi Akashi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1555-1564
Number of pages10
JournalMolecular Cancer Therapeutics
Volume18
Issue number9
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

G-Protein-Coupled Receptors
Multiple Myeloma
T-Lymphocytes
Antibodies
Therapeutics
Hematopoietic Stem Cells
Plasma Cells
Heterografts
Bone Marrow Cells
B-Lymphocytes
Antigens
Survival
Growth
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Anti-GPRC5D/CD3 bispecific T-cell-redirecting antibody for the treatment of multiple myeloma. / Kodama, Tatsushi; Kochi, Yu; Nakai, Waka; Mizuno, Hideaki; Baba, Takeshi; Habu, Kiyoshi; Sawada, Noriaki; Tsunoda, Hiroyuki; Shima, Takahiro; Miyawaki, Kohta; Kikushige, Yoshikane; Mori, Yasuo; Miyamoto, Toshihiro; Maeda, Takahiro; Akashi, Koichi.

In: Molecular Cancer Therapeutics, Vol. 18, No. 9, 01.01.2019, p. 1555-1564.

Research output: Contribution to journalArticle

Kodama, Tatsushi ; Kochi, Yu ; Nakai, Waka ; Mizuno, Hideaki ; Baba, Takeshi ; Habu, Kiyoshi ; Sawada, Noriaki ; Tsunoda, Hiroyuki ; Shima, Takahiro ; Miyawaki, Kohta ; Kikushige, Yoshikane ; Mori, Yasuo ; Miyamoto, Toshihiro ; Maeda, Takahiro ; Akashi, Koichi. / Anti-GPRC5D/CD3 bispecific T-cell-redirecting antibody for the treatment of multiple myeloma. In: Molecular Cancer Therapeutics. 2019 ; Vol. 18, No. 9. pp. 1555-1564.
@article{15f43b0312694c4885e9890731a4751c,
title = "Anti-GPRC5D/CD3 bispecific T-cell-redirecting antibody for the treatment of multiple myeloma",
abstract = "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.",
author = "Tatsushi Kodama and Yu Kochi and Waka Nakai and Hideaki Mizuno and Takeshi Baba and Kiyoshi Habu and Noriaki Sawada and Hiroyuki Tsunoda and Takahiro Shima and Kohta Miyawaki and Yoshikane Kikushige and Yasuo Mori and Toshihiro Miyamoto and Takahiro Maeda and Koichi Akashi",
year = "2019",
month = "1",
day = "1",
doi = "10.1158/1535-7163.MCT-18-1216",
language = "English",
volume = "18",
pages = "1555--1564",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

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

PY - 2019/1/1

Y1 - 2019/1/1

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

VL - 18

SP - 1555

EP - 1564

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 9

ER -