Shedding blocking agents with increased stability
AssigneeBiond Biologics Ltd.
InventorsMotti Hakim, Anna Fridman-Dror, Ilana Mandel, Tehila Ben-Moshe, Yair Sapir, Avidor Shulman, Lilach Chen Zeltsburg, Ayala Lewkowicz
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Abstract
Agents comprising at least two moieties separated by a linker, wherein a first moiety binds mCD28 on a surface of a cell and inhibits proteolytic cleavage of the mCD28 and wherein a second moiety increases stability of the first moiety are provided. Methods of treating cancer and improving immunotherapy comprising administering the agents are also provided.
Claims20
An agent comprising at least two moieties separated by a linker, wherein a first moiety binds membranal CD28 (mCD28) on a surface of a cell and inhibits proteolytic cleavage of said mCD28 and wherein a second moiety increases stability of said first moiety, wherein said linker is at least one of:
- a rigid peptide linker;
- a peptide linker comprising a helix motif;
- comprising at least 15 amino acids;
- a rigid linker comprising at least 30 amino acids;
- comprising at least one cysteine residue;
- and
- comprising at least one C-terminal cysteine residue.
A method of generating an agent, the method comprising either:
- obtaining a first moiety that binds mCD28 on a cell surface and inhibits proteolytic cleavage of said mCD28;
- linking said first moiety to a second moiety by a linker to produce a linked agent, wherein a second moiety increases stability of said first moiety and testing binding of said linked agent to mCD28 on a surface of a cell and inhibition of proteolytic cleavage of said mCD28;
- and
- selecting a linked agent that binds mCD28 on a cell surface and inhibits proteolytic cleavage of said mCD28;
- or
- culturing a host cell comprising one or more vectors comprising a nucleic acid sequence encoding an agent, wherein the nucleic acid sequence is that of an agent that was selected by:
- obtaining a first moiety that binds mCD28 on a cell surface and inhibits proteolytic cleavage of said mCD28;
- linking said first moiety to a second moiety by a linker to produce a linked agent, wherein a second moiety increases stability of said first moiety and testing binding of said linked agent to mCD28 on a surface of a cell and inhibition of proteolytic cleavage of said mCD28;
- and
- selecting a linked agent that binds mCD28 on a cell surface and inhibits proteolytic cleavage of said mCD28;
- thereby generating an agent.
Dependencies are inferred from the claim text.