Agonistic tumor necrosis factor receptor superfamily polypeptides
AssigneeThe General Hospital Corporation
InventorDenise L. Faustman
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Abstract
Described are agonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to stimulate the proliferation of regulatory T cells (Treg cells) and/or myeloid-derived suppressor cells (MDSCs), as well as to inhibit the function of, reduce the proliferation of, and/or directly kill, T effector cells, such as CD8+ T effector cells. The polypeptides, such as antibodies and antigen-binding fragments thereof, of the disclosure can be used, for example, to suppress autoimmunity and inflammation, as well as to promote the protection, healing, preservation, and/or regeneration of a wide variety of tissues and organs, such as tissues and organs containing TNFR2+ cells.
Claims18
An isolaed humanized or chimeric antibody or antigen-binding fragment thereof that binds human tumor necrosis factor receptor 2 (TNFR2), wherein the antibody or antigen-binding fragment thereof comprises the following complementarity determining regions (CDRs):
- (i) a complementarity determining region-heavy chain 1 (CDR-H1) comprising the amino acid sequence GYTFTDYNI (SEQ ID NO:
- 3) or GYTFTDYNL (SEQ ID NO:
- 4);
- (ii) a CDR-H2 comprising the amino acid sequence INPNYDST (SEQ ID NO:
- 10);
- (iii) a CDR-H3 comprising the amino acid sequence CARGNSWYFDV (SEQ ID NO:
- 11);
- (iv) a complementarity determining region-light chain 1 (CDR-L1) comprising the amino acid sequence SSVRY (SEQ ID NO:
- 12);
- (v) a CDR-L2 comprising the amino acid sequence LTS;
- and
- (vi) a CDR-L3 comprising the amino acid sequence CQQWSSNPLT (SEQ ID NO:
- 13).
Dependencies are inferred from the claim text.