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) |
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Pages (from-to) | 512-521 |
Number of pages | 10 |
Journal | Cancer Science |
Volume | 106 |
Issue number | 5 |
DOIs | |
State | Published - May 1 2015 |
Keywords
- Bispecific antibodies
- Immunotherapy
- Multiple myeloma
- Natural killer cells
- T cells
ASJC Scopus subject areas
- Oncology
- Cancer Research