Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer
Hirofumi Mikami
1
,
Shu Feng
2
,
Yutaka Matsuda
3
,
Shinya Ishii
1
,
Sotaro Naoi
2
,
Yumiko Azuma
1
,
Hiroaki Nagano
2
,
Kentaro Asanuma
1
,
Yoko Kayukawa
1
,
Toshiaki Tsunenari
1
,
Shogo Kamikawaji
1
,
Ryutaro Iwabuchi
1
,
Junko Shinozuka
1
,
Masaki Yamazaki
1
,
Haruka Kuroi
1
,
Samantha Shu Wen Ho
2
,
Siok Wan Gan
2
,
Priyanka Chichili
2
,
Chai Ling Pang
2
,
Chiew Ying Yeo
2
,
Shun Shimizu
1
,
Naoka Hironiwa
2
,
Yasuko Kinoshita
1
,
Yuichiro Shimizu
1
,
Akihisa Sakamoto
1
,
Masaru Muraoka
1
,
Noriyuki Takahashi
2
,
Tatsuya Kawa
1
,
Hirotake Shiraiwa
1
,
Futa Mimoto
2
,
Kenji Kashima
1
,
Mika Kamata Sakurai
1
,
Shumpei Ishikawa
4
,
Hiroyuki Aburatani
5
,
Takehisa Kitazawa
1
,
Tomoyuki Igawa
6
1
1Research Division, Chugai Pharmaceutical, Yokohama, Kanagawa, Japan.
|
2
2Research Division, Chugai Pharmabody Research, Singapore, Singapore.
|
3
3Project & Lifecycle Management Unit, Chugai Pharmaceutical, Chuo-ku, Tokyo, Japan.
|
6
6Translational Research Division, Chugai Pharmaceutical, Chuo-ku, Tokyo, Japan.
|
Publication type: Journal Article
Publication date: 2024-04-02
scimago Q1
wos Q1
SJR: 3.630
CiteScore: 12.8
Impact factor: 8.2
ISSN: 23266066, 23266074
PubMed ID:
38558120
Cancer Research
Immunology
Abstract
Small-cell lung cancer (SCLC) is an aggressive cancer for which immune checkpoint inhibitors (ICI) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives for ICI-resistant tumors, but not all patients with SCLC are responsive. Herein, to integrate CD137 costimulatory function into a T-cell engager format and thereby augment therapeutic efficacy, we generated a CD3/CD137 dual-specific Fab and engineered a DLL3-targeted trispecific antibody (DLL3 trispecific). The CD3/CD137 dual-specific Fab was generated to competitively bind to CD3 and CD137 to prevent DLL3-independent cross-linking of CD3 and CD137, which could lead to systemic T-cell activation. We demonstrated that DLL3 trispecific induced better tumor growth control and a marked increase in the number of intratumoral T cells compared with a conventional DLL3-targeted bispecific T-cell engager. These findings suggest that DLL3 trispecific can exert potent efficacy by inducing concurrent CD137 costimulation and provide a promising therapeutic option for SCLC.
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Metrics
18
Total citations:
18
Citations from 2024:
18
(100%)
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MLA
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GOST
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Mikami H. et al. Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer // Cancer immunology research. 2024. Vol. 12. No. 6. p. OF1-OF12.
GOST all authors (up to 50)
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Mikami H., Feng S., Matsuda Y., Ishii S., Naoi S., Azuma Y., Nagano H., Asanuma K., Kayukawa Y., Tsunenari T., Kamikawaji S., Iwabuchi R., Shinozuka J., Yamazaki M., Kuroi H., Ho S. S. W., Gan S. W., Chichili P., Pang C. L., Yeo C. Y., Shimizu S., Hironiwa N., Kinoshita Y., Shimizu Y., Sakamoto A., Muraoka M., Takahashi N., Kawa T., Shiraiwa H., Mimoto F., Kashima K., Kamata Sakurai M., Ishikawa S., Aburatani H., Kitazawa T., Igawa T. Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer // Cancer immunology research. 2024. Vol. 12. No. 6. p. OF1-OF12.
Cite this
RIS
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TY - JOUR
DO - 10.1158/2326-6066.cir-23-0638
UR - https://aacrjournals.org/cancerimmunolres/article/12/6/719/745447/Engineering-CD3-CD137-Dual-Specificity-into-a-DLL3
TI - Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer
T2 - Cancer immunology research
AU - Mikami, Hirofumi
AU - Feng, Shu
AU - Matsuda, Yutaka
AU - Ishii, Shinya
AU - Naoi, Sotaro
AU - Azuma, Yumiko
AU - Nagano, Hiroaki
AU - Asanuma, Kentaro
AU - Kayukawa, Yoko
AU - Tsunenari, Toshiaki
AU - Kamikawaji, Shogo
AU - Iwabuchi, Ryutaro
AU - Shinozuka, Junko
AU - Yamazaki, Masaki
AU - Kuroi, Haruka
AU - Ho, Samantha Shu Wen
AU - Gan, Siok Wan
AU - Chichili, Priyanka
AU - Pang, Chai Ling
AU - Yeo, Chiew Ying
AU - Shimizu, Shun
AU - Hironiwa, Naoka
AU - Kinoshita, Yasuko
AU - Shimizu, Yuichiro
AU - Sakamoto, Akihisa
AU - Muraoka, Masaru
AU - Takahashi, Noriyuki
AU - Kawa, Tatsuya
AU - Shiraiwa, Hirotake
AU - Mimoto, Futa
AU - Kashima, Kenji
AU - Kamata Sakurai, Mika
AU - Ishikawa, Shumpei
AU - Aburatani, Hiroyuki
AU - Kitazawa, Takehisa
AU - Igawa, Tomoyuki
PY - 2024
DA - 2024/04/02
PB - American Association for Cancer Research (AACR)
SP - OF1-OF12
IS - 6
VL - 12
PMID - 38558120
SN - 2326-6066
SN - 2326-6074
ER -
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@article{2024_Mikami,
author = {Hirofumi Mikami and Shu Feng and Yutaka Matsuda and Shinya Ishii and Sotaro Naoi and Yumiko Azuma and Hiroaki Nagano and Kentaro Asanuma and Yoko Kayukawa and Toshiaki Tsunenari and Shogo Kamikawaji and Ryutaro Iwabuchi and Junko Shinozuka and Masaki Yamazaki and Haruka Kuroi and Samantha Shu Wen Ho and Siok Wan Gan and Priyanka Chichili and Chai Ling Pang and Chiew Ying Yeo and Shun Shimizu and Naoka Hironiwa and Yasuko Kinoshita and Yuichiro Shimizu and Akihisa Sakamoto and Masaru Muraoka and Noriyuki Takahashi and Tatsuya Kawa and Hirotake Shiraiwa and Futa Mimoto and Kenji Kashima and Mika Kamata Sakurai and Shumpei Ishikawa and Hiroyuki Aburatani and Takehisa Kitazawa and Tomoyuki Igawa},
title = {Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer},
journal = {Cancer immunology research},
year = {2024},
volume = {12},
publisher = {American Association for Cancer Research (AACR)},
month = {apr},
url = {https://aacrjournals.org/cancerimmunolres/article/12/6/719/745447/Engineering-CD3-CD137-Dual-Specificity-into-a-DLL3},
number = {6},
pages = {OF1--OF12},
doi = {10.1158/2326-6066.cir-23-0638}
}
Cite this
MLA
Copy
Mikami, Hirofumi, et al. “Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer.” Cancer immunology research, vol. 12, no. 6, Apr. 2024, pp. OF1-OF12. https://aacrjournals.org/cancerimmunolres/article/12/6/719/745447/Engineering-CD3-CD137-Dual-Specificity-into-a-DLL3.