Senescent cell-associated antigen-binding domains, antibodies and chimeric antigen receptors comprising the same, and uses thereof
AssigneeStarkAge Therapeutics
InventorsMüge Ogrunc, Thierry Mathieu
Life of this patent
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Abstract
Disclosed are senescent cell-associated antigen-binding domain and related antibodies and related chimeric antigen receptors. In addition, disclosed are DPP4-binding domains and related antibodies and related chimeric antigen receptors. Also disclosed are methods for treating, preventing or alleviating senescence-related diseases or disorders. Methods for depleting and/or killing senescent cells are also disclosed.
Claims12
A method of treating or alleviating a senescence-related disease or disorder in a subject in need thereof, wherein said senescence-related disease or disorder is a cancer comprising DPP4-expressing cells or a fibrotic disease comprising DPP4-expressing cells, the method comprising administering to the subject a composition comprising:
- an isolated antibody or antigen-binding fragment thereof comprising a DPP4-binding domain;
- and/or
- an immune cell engineered to express at its surface a chimeric antigen receptor (CAR) comprising:
- at least one extracellular binding domain, comprising said DPP4-binding domain,
- an extracellular spacer domain,
- a transmembrane domain,
- optionally, at least one costimulatory domain, and
- at least one intracellular signaling domain;
- and/or
- a population of immune cells comprising a plurality of said engineered immune cells,
- wherein said DPP4-binding domain comprises a combination of three heavy chain variable region (HCVR)'s complementary-determining regions (CDRs) and three light chain variable region (LCVR)'s CDRs, said combination being as defined in any row of the table below, wherein the CDRs are defined by their SEQ ID NO:
- VH-
- VH-
- VH-
- VL-
- VL-
- VL-
- Clone’s name
- CDR1
- CDR2
- CDR3
- CDR1
- CDR2
- CDR3
- 5826-13-R3A-A10
- 107
- 119
- 137
- 146
- 157
- 170
- 5826-13-R3A-B1
- 108
- 120
- 138
- 147
- 158
- 171
- 5826-13-R3A-B3
- 108
- 121
- 138
- 147
- 159
- 171
- 5826-13-R3A-D5
- 109
- 122
- 139
- 148
- 160
- 172
- 5826-13-R3A-D6
- 108
- 123
- 138
- 149
- 159
- 171
- 5826-13-R4A-E2
- 108
- 124
- 138
- 147
- 159
- 171
- 5826-13-R4A-E6
- 110
- 125
- 140
- 146
- 161
- 170
- 5826-13-R4A-E9
- 108
- 126
- 141
- 149
- 159
- 171
- 5826-13-R4A-F10
- 108
- 126
- 138
- 150
- 159
- 171
- 5826-13-R4A-G11
- 108
- 126
- 138
- 150
- 159
- 171
- 5826-13-R4A-G12
- 111
- 127
- 138
- 151
- 159
- 171
- 5826-13-R4A-H1
- 110
- 128
- 140
- 146
- 162
- 170
- 5826-13-R4A-H2
- 108
- 126
- 141
- 149
- 159
- 171
- 5826-13-R4A-H3
- 108
- 126
- 138
- 149
- 159
- 173
- 5826-13-R4A-H4
- 112
- 125
- 140
- 146
- 162
- 170
- 5826-13-R4A-H5
- 108
- 127
- 138
- 147
- 159
- 171
- 5826-13-R4A-H6
- 108
- 127
- 142
- 147
- 159
- 171
- 5826-13-R4A-H9
- 108
- 123
- 138
- 149
- 159
- 171
- 5826-13-R4A-H10
- 110
- 125
- 140
- 146
- 162
- 170
- 5826-13-R4A-H11
- 110
- 128
- 140
- 146
- 162
- 170
- 5826-13-R4A-H12
- 110
- 125
- 140
- 146
- 163
- 170
Dependencies are inferred from the claim text.