Treatment of kidney injury
Methods of treating and preventing kidney injury through inhibiting interleukin 11 (IL-11)-mediated signalling are disclosed, as well as agents for use in such methods.
1. A method of treating chemically-induced kidney injury, the method comprising administering a therapeutically effective amount of an anti-IL-11 antibody or an antigen-binding fragment thereof which is an antagonist of IL-11-mediated signalling to a subject.
2. The method according to claim 1 , wherein the chemically-induced kidney injury is acute kidney injury.
3. The method according to claim 1 , wherein the chemically-induced kidney injury is nephrotoxicity.
4. The method according to claim 1 , wherein the chemically-induced kidney injury is drug-induced kidney injury or ischemia-induced kidney injury.
5. The method according to claim 1 , wherein the chemically-induced kidney injury is cisplatin-induced kidney injury or cisplatin-induced nephrotoxicity.
6. The method according to claim 1 , wherein the chemically-induced kidney injury is characterised by damage to tubular epithelial cells (TECs).
7. The method according to claim 1 , wherein the anti-IL-11 antibody or an antigen-binding fragment thereof which is an antagonist of IL-11-mediated signalling prevents or reduces the binding of interleukin 11 (IL-11) to a receptor for interleukin 11 (IL-11R).
8. The method according to claim 1 , wherein the anti-IL-11 antibody or antigen-binding fragment thereof which is an antagonist of IL-11-mediated signalling, comprises:
(i) a heavy chain variable (VH) region incorporating the following CDRs:
HC-CDR1 having the amino acid sequence of SEQ ID NO: 34;
HC-CDR2 having the amino acid sequence of SEQ ID NO: 35; and
HC-CDR3 having the amino acid sequence of SEQ ID NO: 36; and
(ii) a light chain variable (VL) region incorporating the following CDRs:
LC-CDR1 having the amino acid sequence of SEQ ID NO: 37;
LC-CDR2 having the amino acid sequence of SEQ ID NO: 38; and
LC-CDR3 having the amino acid sequence of SEQ ID NO:39.
9. The method according to claim 1 , wherein the anti-IL-11 antibody or antigen-binding fragment thereof which is an antagonist of IL-11-mediated signalling, comprises:
(i) a heavy chain variable (VH) region incorporating the following CDRs:
HC-CDR1 having the amino acid sequence of SEQ ID NO: 40;
HC-CDR2 having the amino acid sequence of SEQ ID NO: 41; and
HC-CDR3 having the amino acid sequence of SEQ ID NO: 42; and
(ii) a light chain variable (VL) region incorporating the following CDRs:
LC-CDR1 having the amino acid sequence of SEQ ID NO: 43;
LC-CDR2 having the amino acid sequence of SEQ ID NO: 44; and
LC-CDR3 having the amino acid sequence of SEQ ID NO: 45.
10. The method according to claim 1 , wherein the method comprises administering the anti-IL-11 antibody or antigen-binding fragment thereof which is an antagonist of IL-11-mediated signalling to a subject in which expression of interleukin 11 (IL-11) or a receptor for IL-11 (IL-11R) is upregulated.
11. The method according to claim 1 , wherein the method further comprises determining whether expression of interleukin 11 (IL-11) or a receptor for IL-11 (IL-11R) is upregulated in the subject and administering the anti-IL-11 antibody or antigen-binding fragment thereof which is an antagonist of IL-11-mediated signalling, to a subject in which expression of interleukin 11 (IL-11) or a receptor for IL-11 (IL-11R) is upregulated.