Bispecific antibody binding to human CD26 and human CD3, production method therefor and use thereof
Inventors
Ma, Yong • CAO, Peipei • WANG, Anliang
Assignees
GENSUN INSTITUTE OF BIOMEDICINE Co Ltd • Zonhon Biopharma Institute Inc
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Publication Number
US-10752686-B2
Publication Date
2020-08-25
Expiration Date
Abstract
Described is a bispecific antibody, and a method for producing the bispecific antibody. The bispecific antibody can be used in the preparation of a drug for treating a tumor with high cell expression of CD26. The antibody specifically hinds to human CD26 and human CD3 at the same time.
Core Innovation
The invention relates to an anti-human CD26×anti-human CD3 bispecific antibody molecule comprising a variable domain fragment that specifically binds to human CD26 and a variable domain fragment that specifically binds to human CD3. The CD26-binding variable domain fragment comprises a first heavy chain variable domain comprising SEQ ID NO: 1 and a first light chain variable domain comprising SEQ ID NO: 2, and the CD3-binding variable domain fragment comprises a second heavy chain variable domain comprising SEQ ID NO: 4 and a second light chain variable domain comprising SEQ ID NO: 5.
The invention defines structural arrangements of variable domains in the bispecific antibody molecule by specifying adjacency of variable domains and the ordering of polypeptide chains from N-terminus to C-terminus. The document describes engineered fusion constructs with distinct heavy/light domain orders, including ZHB BsAb-1, ZHB BsAb-2, ZHB BsAb-3, and ZHB BsAb-4, presented as single-chain or IgG-like formats.
The described concept is to generate CD26-high tumor cell killing by bringing CD3-positive cells into functional interaction with CD26-binding sites. Functional cytotoxicity results are reported showing CD26×CD3 bispecific-mediated killing of CD26-high tumor cells by PBMCs or T cells, with improved activity over single anti-CD26 scFv and anti-CD3 scFv controls and selective lack of effect on CD26-negative control cells.
Claims Coverage
The independent claim covers a CD26×CD3 bispecific antibody molecule defined by specific CD26- and CD3-binding variable domain fragments using specified SEQ ID NOs. Dependent claims refine the structural arrangement of the variable domains and further narrow to treatment of CD26-high tumors, including specific tumor types.
Bispecific antibody molecule with human CD26 and human CD3 binding variable domain fragments defined by SEQ ID NOs
A bispecific antibody molecule comprising a variable domain fragment that specifically binds to human CD26 and a variable domain fragment that specifically binds to human CD3, where the CD26-binding variable domain fragment includes a first heavy chain variable domain comprising SEQ ID NO: 1 and a first light chain variable domain comprising SEQ ID NO: 2, and the CD3-binding variable domain fragment includes a second heavy chain variable domain comprising SEQ ID NO: 4 and a second light chain variable domain comprising SEQ ID NO: 5.
Adjacent placement of variable domains in the bispecific antibody molecule
A bispecific antibody molecule wherein either the first and second heavy chain variable domains are arranged adjacent to each other or the first and second light chain variable domains are arranged adjacent to each other.
N-terminus to C-terminus ordering of heavy/light variable domains
A bispecific antibody molecule with a polypeptide chain ordered from N-terminus to C-terminus comprising specified combinations of first/second light chain variable domains and first/second heavy chain variable domains.
Treating tumors with high CD26 expression by administering the CD26×CD3 bispecific antibody
A method for treating a tumor with high CD26 expression by administering the bispecific antibody molecule to a subject in need.
Tumor treatment limited to renal cancer, prostatic cancer, colon cancer, or mesothelioma
The method where the tumor is renal cancer, prostatic cancer, colon cancer, or mesothelioma.
Overall, the claim set covers a CD26×CD3 bispecific antibody defined by specific CD26- and CD3-binding variable domain fragments, with additional structural restrictions on variable domain adjacency and N- to C-terminal ordering, and it narrows to treating CD26-high tumors, further specified to renal, prostatic, colon, or mesothelioma.
Stated Advantages
Improved activity of CD26×CD3 bispecifics over single anti-CD26 scFv and anti-CD3 scFv controls.
Selective lack of effect on CD26-negative control cells.
High-affinity binding to CD26.
Suitability for large-scale eukaryotic expression as described in the document content.
Absence of Fc-related features as described in the document content.
Improved immunogenicity/quality control relative to Fc-containing humanized IgGs as stated in the document content.
Documented Applications
Use in treating a tumor with high CD26 expression by administering the CD26×CD3 bispecific antibody to a subject in need.
Tumor treatment applications are described for renal cancer, prostatic cancer, colon cancer, and mesothelioma.
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