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 . A method of inhibiting a human Tim-3 or inhibiting Tim-3-mediated T cell suppression in a subject comprising administering an effective amount of an antibody or antigen-binding fragment thereof comprising:
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
b) 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 method of claim 1 , wherein the subject has a cancer.
3 . A method of treating a cancer in a subject comprising administering to the subject an effective amount of an antibody or antigen-binding fragment thereof comprising:
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
b) 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 method of claim 3 , wherein the cancer is a human Tim-3-positive cancer.
5 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof binds to an IgV domain of the human Tim-3 or IgV mucin-stalk of the human Tim-3.
6 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises 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).
7 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises 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).
8 . The method of claim 2 , wherein the cancer is a hematologic malignancy, a cancer of lung, gastric, head or neck cancer, schwannoma, melanoma, or follicular B-cell non-Hodgkin lymphoma.
9 . The method of claim 3 , wherein the antibody or antigen-binding fragment thereof binds to an IgV domain of the human Tim-3 or IgV mucin-stalk of the human Tim-3.
10 . The method of claim 3 , wherein the antibody or antigen-binding fragment thereof comprises 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).
11 . The method of claim 3 , wherein the antibody or antigen-binding fragment thereof comprises 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).
12 . The method of claim 3 , wherein the cancer is a hematologic malignancy, a cancer of lung, gastric, head or neck cancer, schwannoma, melanoma, or follicular B-cell non-Hodgkin lymphoma.
13 . The method of claim 3 , wherein the subject is receiving an anti-PD-1 or anti-PD-L1 or anti-CTLA4 therapy.
14 . A method of detecting a human Tim-3 positive cell in a subject comprising administering to the subject an effective amount of an antibody or antigen-binding fragment thereof comprising:
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
b) 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);
further comprising a detectable marker conjugated thereto, in an amount effective to label the human Tim-3 positive cell.
15 . The method of claim 14 , wherein the antibody or antigen-binding fragment thereof binds to an IgV domain of the human Tim-3 or IgV mucin-stalk of the human Tim-3.
16 . The method of claim 14 , wherein the antibody or antigen-binding fragment thereof comprises 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).
17 . The method of claim 14 , wherein the antibody or antigen-binding fragment thereof comprises 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).
18 . The method of claim 14 , wherein the label is detected by imaging.
19 . The method of claim 14 , wherein the human Tim-3 positive cell is a cancer cell.
20 . The method of claim 19 , wherein the cancer is a hematologic malignancy, a cancer of lung, gastric, head or neck cancer, schwannoma, melanoma, or follicular B-cell non-Hodgkin lymphoma.