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

Cancer Sci. 2015 May;106(5):512-21. doi: 10.1111/cas.12631. Epub 2015 Mar 13.

Authors

Jianxuan Zou^{1

2}, Dan Chen^{1

2}, Yunhui Zong³, Sisi Ye³, Jinle Tang^{1

2}, Huimin Meng^{1

2}, Gangli An^{1

2}, Xingding Zhang³, Lin Yang^{1

2}

Affiliations

¹ The Cyrus Tang Hematology Center, Soochow University, Suzhou, China.
² Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
³ Suzhou Cancer Immunotherapy and Diagnosis Engineering Center, Suzhou, China.

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.

Keywords: Bispecific antibodies; T cells; immunotherapy; multiple myeloma; natural killer cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Antibodies, Bispecific / genetics
Antibodies, Bispecific / immunology*
Antibodies, Bispecific / metabolism
Antigens, CD / metabolism
Antigens, Differentiation, T-Lymphocyte / metabolism
CD3 Complex / genetics
CD3 Complex / immunology
CD3 Complex / metabolism
Cell Line, Tumor
Humans
Immunoglobulin G / genetics
Immunoglobulin G / immunology
Immunotherapy / methods*
Interleukin-2 Receptor alpha Subunit / metabolism
Killer Cells, Natural / immunology
Killer Cells, Natural / metabolism
Lectins, C-Type / metabolism
Mice, SCID
Molecular Sequence Data
Multiple Myeloma / immunology
Multiple Myeloma / therapy*
Receptors, IgG / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / immunology
Recombinant Proteins / metabolism
Single-Chain Antibodies / genetics
Single-Chain Antibodies / immunology*
Syndecan-1 / genetics
Syndecan-1 / immunology
Syndecan-1 / metabolism
T-Lymphocytes / immunology
Xenograft Model Antitumor Assays

Substances

Antibodies, Bispecific
Antigens, CD
Antigens, Differentiation, T-Lymphocyte
CD3 Complex
CD69 antigen
IL2RA protein, human
Immunoglobulin G
Interleukin-2 Receptor alpha Subunit
Lectins, C-Type
Receptors, IgG
Recombinant Proteins
SDC1 protein, human
Single-Chain Antibodies
Syndecan-1