Immunotherapy based on bispecific T-cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma

Jianxuan Zou; Dan Chen; Yunhui Zong; Sisi Ye; Jinle Tang; Huimin Meng; Gangli An; Xingding Zhang; Lin Yang

doi:10.1111/cas.12631

Immunotherapy based on bispecific T-cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma

Jianxuan Zou, Dan Chen, Yunhui Zong, Sisi Ye, Jinle Tang, Huimin Meng, Gangli An, Xingding Zhang, Lin Yang^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

Abstract

Bispecific antibodies play an important role in immunotherapy. They have received intense interest from pharmaceutical enterprises. The first antibody drug, OKT3 (muromonab-CD3), showed great performance in clinical treatment. We have successfully developed a single-chain variable fragment (ScFv) combination of anti-CD3 ScFv and anti-CD138 ScFv with the hIgG1 Fc (hIgFc) sequence. The novel bispecific T-cell engager (BiTE) with an additional hIgFc (BiTE-hIgFc, STL001) can target T cells, natural killer cells, and multiple myeloma cells (RPMI-8226 or U266). In addition, BiTE-hIgFc (STL001) has nanomolar-level affinity to recombinant human CD138 protein and shows more potent antitumor activity against RPMI-8226 cells than that of separate aCD3-ScFv-hIgFc and aCD138-ScFv-hIgFc, or the isotype mAb in vitro or in vivo. The world's first CD138/CD3 BiTE-hIgFc targeting T cells, natural killer cells and multiple myeloma cells simultaneously has nanomolar-level affinity to recombinant hCD138 protein and has shown potent antitumor activity against RPMI-8226 tumor cells in vitro and in vivo.

Original language	English (US)
Pages (from-to)	512-521
Number of pages	10
Journal	Cancer Science
Volume	106
Issue number	5
DOIs	https://doi.org/10.1111/cas.12631
State	Published - May 1 2015

Keywords

Bispecific antibodies
Immunotherapy
Multiple myeloma
Natural killer cells
T cells

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/cas.12631

Cite this

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title = "Immunotherapy based on bispecific T-cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma",

abstract = "Bispecific antibodies play an important role in immunotherapy. They have received intense interest from pharmaceutical enterprises. The first antibody drug, OKT3 (muromonab-CD3), showed great performance in clinical treatment. We have successfully developed a single-chain variable fragment (ScFv) combination of anti-CD3 ScFv and anti-CD138 ScFv with the hIgG1 Fc (hIgFc) sequence. The novel bispecific T-cell engager (BiTE) with an additional hIgFc (BiTE-hIgFc, STL001) can target T cells, natural killer cells, and multiple myeloma cells (RPMI-8226 or U266). In addition, BiTE-hIgFc (STL001) has nanomolar-level affinity to recombinant human CD138 protein and shows more potent antitumor activity against RPMI-8226 cells than that of separate aCD3-ScFv-hIgFc and aCD138-ScFv-hIgFc, or the isotype mAb in vitro or in vivo. The world's first CD138/CD3 BiTE-hIgFc targeting T cells, natural killer cells and multiple myeloma cells simultaneously has nanomolar-level affinity to recombinant hCD138 protein and has shown potent antitumor activity against RPMI-8226 tumor cells in vitro and in vivo.",

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author = "Jianxuan Zou and Dan Chen and Yunhui Zong and Sisi Ye and Jinle Tang and Huimin Meng and Gangli An and Xingding Zhang and Lin Yang",

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AU - Zou, Jianxuan

AU - Chen, Dan

AU - Zong, Yunhui

AU - Ye, Sisi

AU - Tang, Jinle

AU - Meng, Huimin

AU - An, Gangli

AU - Zhang, Xingding

AU - Yang, Lin

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Immunotherapy based on bispecific T-cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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