Compositions and methods for the treatment of immune related diseases
The present invention relates to compositions and methods of using those compositions for the diagnosis and treatment of immune related diseases.
1. A method for increasing immune system function and/or activity in a subject, the method comprising administering to the subject an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36,
wherein the anti-TIGIT antibody, or antigen-binding fragment thereof, decreases the binding of TIGIT to one or more of PVR, PVRL3, and PVRL2.
2. A method of treating and/or lessening the severity of an immune-related disease relating to aberrant immune cell response in a subject, the method comprising administering to the subject an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36,
wherein the anti-TIGIT antibody, or antigen-binding fragment thereof, decreases the activity of TIGIT in the subject, and wherein the immune-related disease is cancer.
3. The method of claim 1 or 2 , wherein the subject is a mammal.
4. The method of claim 3 , wherein the mammal is a human.
5. A method of increasing or stimulating proliferation of a T cell or proinflammatory cytokine release by a dendritic cell in a subject, the method comprising administering to the subject an antagonist of TIGIT activity, wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.
6. A method of increasing or stimulating proliferation of a T cell or proinflammatory cytokine release by a dendritic cell in vitro, wherein the method comprises contacting a co-culture of T cells and dendritic cells with an antagonist of TIGIT activity, and wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.
7. The method of claim 5 or 6 , wherein the T cell is an activated T cell.
8. The method of claim 5 or 6 , wherein the method blocks regulatory T (T reg ) cell-mediated suppression of T cell proliferation.
9. A method of stimulating a CD226-PVR interaction and/or a CD96-PVR interaction in a subject, the method comprising administering to the subject an antagonist of TIGIT activity, wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.
10. A method of increasing or stimulating a T cell immune response in a subject, the method comprising administering to the subject an antagonist of TIGIT activity, wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.
11. A method of increasing or stimulating proinflammatory cytokine production from a dendritic cell in a subject, the method comprising administering to the subject an antagonist of TIGIT activity, wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.
12. A method of stimulating a CD226-PVR interaction and/or a CD96-PVR interaction in vitro, wherein the method comprises contacting a co-culture of T cells and dendritic cells with an antagonist of TIGIT activity, and wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.
13. A method of increasing or stimulating a T cell immune response in vitro, wherein the method comprises contacting a co-culture of T cells and dendritic cells with an antagonist of TIGIT activity, and wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.
14. A method of increasing or stimulating proinflammatory cytokine production from a dendritic cell in vitro, wherein the method comprises contacting a co-culture of T cells and dendritic cells with an antagonist of TIGIT activity, and wherein the antagonist of TIGIT activity is an anti-TIGIT antibody, or antigen-binding fragment thereof, comprising:
(a) a light chain comprising an HVR-L1 comprising SEQ ID NO: 23, an HVR-L2 comprising SEQ ID NO: 24, and an HVR-L3 comprising SEQ ID NO: 25, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 26, an HVR-H2 comprising SEQ ID NO: 27, and an HVR-H3 comprising SEQ ID NO: 28, or
(b) a light chain comprising an HVR-L1 comprising SEQ ID NO: 31, an HVR-L2 comprising SEQ ID NO: 32, and an HVR-L3 comprising SEQ ID NO: 33, and a heavy chain comprising an HVR-H1 comprising SEQ ID NO: 34, an HVR-H2 comprising SEQ ID NO: 35, and an HVR-H3 comprising SEQ ID NO: 36.
15. The method of any one of claims 1 , 9 , 5 , 10 , 11 , 2 , and 12 - 14 , wherein the anti-TIGIT antibody, or antigen-binding fragment thereof, comprises:
(a) a light chain comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 21, and the heavy chain comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 22, or
(b) a light chain comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 29, and the heavy chain comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO: 30.
16. The method of claim 15 , wherein the anti-TIGIT antibody, or antigen-binding fragment thereof, comprises:
(a) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 21, and the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 22, or
(b) a light chain comprising the amino acid sequence set forth in SEQ ID NO: 29, and the heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 30.
17. The method of claim 16 , wherein the anti-TIGIT antibody or antigen-binding fragment is selected from a humanized antibody, a chimeric antibody, a bispecific antibody, a heteroconjugate antibody, and an immunotoxin.