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

Research output: Contribution to journalArticle

24 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 languageEnglish (US)
Pages (from-to)512-521
Number of pages10
JournalCancer Science
Volume106
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • Bispecific antibodies
  • Immunotherapy
  • Multiple myeloma
  • Natural killer cells
  • T cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Zou, J., Chen, D., Zong, Y., Ye, S., Tang, J., Meng, H., An, G., Zhang, X., & Yang, L. (2015). Immunotherapy based on bispecific T-cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma. Cancer Science, 106(5), 512-521. https://doi.org/10.1111/cas.12631