Figure S2 from Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer

Mikami, Hirofumi; Feng, Shu; Matsuda, Yutaka; Ishii, Shinya; Naoi, Sotaro; Azuma, Yumiko; Nagano, Hiroaki; Asanuma, Kentaro; Kayukawa, Yoko; Tsunenari, Toshiaki; Kamikawaji, Shogo; Iwabuchi, Ryutaro; Shinozuka, Junko; Yamazaki, Masaki; Kuroi, Haruka; Ho, Samantha Shu Wen; Gan, Siok Wan; Chichili, Priyanka; Pang, Chai Ling; Yeo, Chiew Ying; Shimizu, Shun; Hironiwa, Naoka; Kinoshita, Yasuko; Shimizu, Yuichiro; Sakamoto, Akihisa; Muraoka, Masaru; Takahashi, Noriyuki; Kawa, Tatsuya; Shiraiwa, Hirotake; Mimoto, Futa; Kashima, Kenji; Kamata-Sakurai, Mika; Ishikawa, Shumpei; Aburatani, Hiroyuki; Kitazawa, Takehisa; Igawa, Tomoyuki

doi:10.1158/2326-6066.25964679.v1

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Figure S2 from Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer

journal contribution

posted on 2024-06-04, 07:23 authored by Hirofumi Mikami, Shu Feng, Yutaka Matsuda, Shinya Ishii, Sotaro Naoi, Yumiko Azuma, Hiroaki Nagano, Kentaro Asanuma, Yoko Kayukawa, Toshiaki Tsunenari, Shogo Kamikawaji, Ryutaro Iwabuchi, Junko Shinozuka, Masaki Yamazaki, Haruka Kuroi, Samantha Shu Wen Ho, Siok Wan Gan, Priyanka Chichili, Chai Ling Pang, Chiew Ying Yeo, Shun Shimizu, Naoka Hironiwa, Yasuko Kinoshita, Yuichiro Shimizu, Akihisa Sakamoto, Masaru Muraoka, Noriyuki Takahashi, Tatsuya Kawa, Hirotake Shiraiwa, Futa Mimoto, Kenji Kashima, Mika Kamata-Sakurai, Shumpei Ishikawa, Hiroyuki Aburatani, Takehisa Kitazawa, Tomoyuki Igawa

Supplementary Figure S2. Overview of the generation of the CD3/CD137 dual-specific Fab

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ARTICLE 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.