Monoclonal antibodies against human tim-3
Provided are anti-human Tim-3 IgV domain-specific antibodies and fragments thereof, as well as methods of use employing such antibodies and/or fragments.
1. An antibody or antigen-binding fragment thereof which binds to an IgV domain of a human Tim-3 (T cell immunoglobulin and mucin-domain containing-3) or IgV mucin-stalk of a human Tim-3, and comprises:
a)
GYSFTGYTIN (SEQ ID NO: 1) (HCDR1);
LFNPYNGGTT (SEQ ID NO: 2 (HCDR2);
ARRYYGYDAMDY (SEQ ID NO: 3) (HCDR3);
KSSQSVLYSSNQKNHLA (SEQ ID NO: 4) (LCDR1);
WASTRES (SEQ ID NO: 5) (LCDR2); and
HQYLSSYT (SEQ ID NO: 6) (LCDR3); or
GFNIKDYYMH (SEQ ID NO: 7) (HCDR1);
WIDPENDNTIY (SEQ ID NO: 8) (HCDR2);
ARDFGYVAWLVY (SEQ ID NO: 9) (HCDR3);
KASQNVDTAVA (SEQ ID NO: 10) (LCDR1);
SASNRYT (SEQ ID NO: 11) (LCDR2); and
QQYSSYPT (SEQ ID NO: 12) (LCDR3).
2. The antibody or antigen-binding fragment thereof of claim 1 comprising:
GYSFTGYTIN (SEQ ID NO: 1) (HCDR1);
LFNPYNGGTT (SEQ ID NO: 2) (HCDR2);
ARRYYGYDAMDY (SEQ ID NO: 3) (HCDR3);
KSSQSVLYSSNQKNHLA (SEQ ID NO: 4) (LCDR1);
WASTRES (SEQ ID NO: 5) (LCDR2); and
HQYLSSYT (SEQ ID NO: 6) (LCDR3).
3. The antibody or antigen-binding fragment thereof of claim 1 comprising:
GFNIKDYYMH (SEQ ID NO: 7) (HCDR1);
WIDPENDNTIY (SEQ ID NO: 8) (HCDR2);
ARDFGYVAWLVY (SEQ ID NO: 9) (HCDR3);
KASQNVDTAVA (SEQ ID NO: 10) (LCDR1);
SASNRYT (SEQ ID NO: 11) (LCDR2); and
QQYSSYPT (SEQ ID NO: 12) (LCDR3).
4. The antibody or antigen-binding fragment thereof of claim 1 , wherein the framework regions of the light and heavy chains have at least 85% identity to human framework regions.
5. The antibody or antigen-binding fragment thereof of claim 1 , which binds to an IgV domain of a human Tim-3 or IgV mucin-stalk of a human Tim-3, with an affinity of 10.0 nM K D or less.
6. The antibody or antigen-binding fragment thereof of claim 5 , which binds to an IgV domain of a human Tim-3 or IgV mucin-stalk of a human Tim-3, with an affinity of 0.5 nM K D or less.
7. The antibody or antigen-binding fragment thereof of claim 1 , which has a human Fc region.
8. The antibody or antigen-binding fragment thereof of claim 5 , which inhibits binding of human Tim-3 to phosphatidylserine expressed on a dexamethasone-treated Jurkat T cell.
9. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is chimeric or humanized.
10. The antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is selected from the group consisting of a monoclonal antibody, an scFv, a Fab fragment, a Fab′fragment, and an F(ab)′fragment.
11. The antibody or antigen-binding fragment thereof of claim 1 , which is linked or conjugated to a therapeutic agent selected from the group consisting of a cytotoxic drug, a radioactive isotope, an immunomodulator, and a second antibody.