Glycan-interacting compounds and methods of use
View Patent ↗The present invention provides glycan-interacting antibodies and methods for producing glycan-interacting antibodies useful in the treatment and prevention of human disease, including cancer. Such glycan-interacting antibodies include monoclonal antibodies, derivatives, and fragments thereof as well as compositions and kits comprising them. Further provided are methods of using glycan-interacting antibodies to target cells and treat disease.
1. A method of reducing tumor volume comprising administering an antibody that specifically binds to sialyl Tn antigen (STn) to a subject, wherein said subject has a tumor comprising STn, wherein said antibody is administered at a dose of from about 0.25 mg/kg to about 25 mg/kg, and wherein said antibody comprises:
a heavy chain variable domain (VH) comprising:
a complementarity determining region (CDR)-H1 comprising the amino acid sequence of SEQ ID NO: 143:
a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146; and
a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 153;
a light chain variable domain (VL) comprising:
a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 161;
a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 123; and
a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 135; and
a conjugated cytotoxic agent,
thereby reducing the volume of said tumor comprising STn in said subject.
2. The method of claim 1 , wherein said antibody is a monoclonal antibody.
3. The method of claim 1 , wherein said antibody comprises an IgG1 isotype.
4. The method of claim 1 , wherein said antibody comprises an IgG2 isotype.
5. The method of claim 1 , wherein said conjugated cytotoxic agent comprises monomethyl auristatin E.
6. The method of claim 1 , wherein tumor volume in said subject is reduced by at least 20%.
7. The method of claim 6 , wherein tumor volume in said subject is reduced by from about 80% to about 99%.
8. The method of claim 7 , wherein said conjugated cytotoxic agent comprises monomethyl auristatin E.
9. A composition comprising:
(a) an antibody that specifically binds to sialyl Tn antigen (STn), said antibody comprising:
a VH comprising:
a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 143;
a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146; and
a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 153; and
a VL comprising:
a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 161;
a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 123; and
a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 135; and
(b) an excipient, said excipient comprising from about 2 mM to about 100 mM citrate and from about 10 mM to about 300 mM NaCl.
10. The composition of claim 9 , wherein said antibody is conjugated to a drug.
11. A method of treating cancer that expresses sialyl Tn antigen (STn) comprising administering a composition to a subject, wherein said subject comprises at least one cancer cell that expresses STn, and wherein said composition comprises:
(a) an antibody that specifically binds to STn comprising:
a VH comprising:
a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 143;
a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146; and
a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 153;
a VL comprising:
a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 161;
a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 123; and
a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 135; and
a conjugated cytotoxic agent; and
(b) an excipient, said excipient comprising from about 2 mM to about 100 mM citrate and from about 10 mM to about 300 mM NaCl,
thereby treating said cancer in said subject.
12. The method of claim 11 , wherein said conjugated cytotoxic agent comprises monomethyl auristatin E.
13. The method of claim 1 , wherein STn is present on the surface of at least one cell of said tumor comprising STn.
14. The method of claim 11 , wherein STn is present on the surface of said at least one cancer cell that expresses STn.
15. A method of treating cancer that expresses sialyl Tn antigen (STn) comprising administering an antibody that specifically binds to STn to a subject, wherein said subject includes at least one cancer cell that expresses cell surface STn, wherein said antibody is administered at a dose of from about 0.25 mg/kg to about 25 mg/kg, and wherein said antibody comprises:
a VH comprising:
a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 143;
a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 146; and
a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 153;
a VL comprising:
a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 161;
a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 123; and
a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 135; and
wherein said antibody comprises an Fc region capable of promoting antibody-dependent cell-mediated cytotoxicity, antibody-dependent cell phagocytosis, and/or complement-dependent cytotoxicity directed against said at least one cancer cell in said subject or wherein said antibody includes a conjugated cytotoxic agent,
thereby treating said cancer in said subject.
16. The method of claim 15 , wherein said antibody includes a conjugated cytotoxic agent, wherein said conjugated cytotoxic agent is conjugated directly or via a linker.
17. The method of claim 16 , wherein said conjugated cytotoxic agent comprises a cytoskeletal inhibitor.
18. The method of claim 17 , wherein said cytoskeletal inhibitor is monomethyl auristatin E.
19. The composition of claim 10 , wherein said drug is conjugated directly or via a linker.
20. The composition of claim 19 , wherein said drug is a cytotoxic agent.
21. The composition of claim 20 , wherein said cytotoxic agent is monomethyl auristatin E.