Adiponectin alone or in combination with extracorporeal photopheresis (ECP) for immune related adverse events of immune checkpoint inhibitors
Adiponectin and adiponectin receptor agonists combined with ECP therapy provide a novel approach to manage immune-related adverse events from ICB therapy, improving treatment outcomes.
Patent Information
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- THERAKOS DEVELOPMENT LTD
- Filing Date
- 2026-04-17
- Publication Date
- 2026-07-10
AI Technical Summary
Current treatments for immune checkpoint blockade (ICB)-induced immune-related adverse events (irAEs) are inadequate, particularly in the context of cancer therapy, necessitating a more effective approach.
A combination therapy using adiponectin and/or adiponectin receptor agonists (ARA) in conjunction with external photodisplacement (ECP) therapy, involving ultraviolet A (UVA) irradiation, to treat immune-related adverse events.
The combination therapy effectively mitigates immune-related adverse events by enhancing treatment efficacy and reducing adverse effects.
Abstract
Description
SP2615933 Abstract: This invention relates to a substance, adiponectin and / or adiponectin receptor agonist (ARA), for treating immune checkpoint blockade (ICB)-induced immune-related adverse events (irAEs) in subjects, wherein the subject preferably receives checkpoint blockade therapy as a cancer treatment. The invention also relates to a combination medicine comprising adiponectin and / or an adiponectin receptor agonist (ARA) and a photosensitizer for use in combination to treat immune checkpoint blockade (ICB)-induced immune-related adverse events (irAEs) in subjects, wherein the treatment further includes external irradiation of a blood sample from the subject with ultraviolet A (UVA), preferably using external photodisplacement (ECP) therapy. Abstract
Claims
CLAIMS1. Adiponectin and / or Adiponectin Receptor Agonist (ARA) for use in the treatment or prevention of immune checkpoint blockade (ICB)-induced immune related adverse events (irAEs) in a subject.
2. Adiponectin and / or ARA for use according to claim 1, wherein the subject is receiving checkpoint blockade therapy.
3. Adiponectin and / or ARA for use according to any one of the preceding claims, wherein Adiponectin and / or ARA is administered at least 1 hour before, during and / or at least one hour after administration of checkpoint blockade therapy.
4. Adiponectin and / or ARA for use according to any one of the preceding claims, wherein the checkpoint blockade therapy comprises administration of at least one antibody, preferably at least two antibodies.
5. Adiponectin and / or ARA for use according to any one of the preceding claims, wherein the at least one antibody is selected from the group comprising cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death- 1 (PD-1) and / or programmed cell death ligand-1 (PD-L1) or Lymphocyte-activation gene 3 (LAG-3).
6. Adiponectin and / or ARA for use according to any one of the preceding claims, wherein irAEs can involve any organ, preferably the gastrointestinal tract, lungs, endocrine glands, skin, and liver.
7. Adiponectin and / or ARA for use according to any one of the preceding claims, wherein the irAE comprise an ICB-induced colitis.
8. Adiponectin and / or ARA for use according to any one of the preceding claims, wherein the administration of Adiponectin and / or ARA reduces ICB-induced colitis.
9. Adiponectin and / or ARA for use according to any one of the preceding claims, wherein the administration of Adiponectin and / or ARA does not interfere with the anti-tumor response induced by the checkpoint blockade therapy, which is preferably an anti-PDl treatment, due to the tissue specific adiponectin induction.
10. Combination medication for use in the treatment of immune checkpoint blockade (ICB)- induced immune related adverse events (irAEs) in a subject, comprising at least two of the following components: a. a photosensitizing agent, and b. Adiponectin and / or Adiponectin Receptor Agonist (ARA), and wherein a blood sample of said subject is subjected to ultraviolet A (UVA) irradiation extracorporeally, preferably to extracorporeal photopheresis (ECP) therapy.
11. The combination medication for use according to claim 10, wherein the photosensitizing agent is a psoralen reagent, preferably 8-methoxypsoralen.
12. The combination medication for use according to claims 10 to 11, wherein the wavelength of the UVA irradiation is from wavelength of 3200 to 4000 angstroms.
13. The combination medication for use according to claims 10 to 12, wherein the subject suffers from cancer.
14. The combination medication for use according to claims 10 to 13, wherein the checkpoint blockade therapy comprises administration of at least one antibody, preferably at least two antibodies.
15. The combination medication for use according to claims 10 to 14, wherein the at least one antibody is selected from the group comprising cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and / or programmed cell death ligand-1 (PD- Ll) or Lymphocyte-activation gene 3 (LAG-3).
16. The combination medication for use according to claims 10 to 15, wherein irAEs can involve any organ, preferably the gastrointestinal tract, lungs, endocrine glands, skin, and liver.
17. The combination medication for use according to claims 10 to 16, wherein the irAE comprises an ICB induced colitis.
18. The combination medication for use according to claims 10 to 17, wherein the combination medication induces an increase of adiponectin, arginase- 1 (Argl) and tolerogenic KLRG1+BTLA+CD47+TOX1OWT cells in inflamed intestines, but not in cancer tissue in said subject.
19. Adiponectin and / or Adiponectin Receptor Agonist (ARA) for use in the treatment of a tumor patient (or: subject suffering from cancer), wherein said patient has developed immune checkpoint blockade (ICB)-induced immune related adverse events (irAEs), wherein said treatment comprises the combined administration of Adiponectin and / or ARA with an anti-tumor immunotherapy, wherein said immunotherapy comprises the administration of immunoregulatory T cells.
20. Adiponectin and / or ARA for use in the treatment of a tumor patient according to the preceding claim, wherein the immunoregulatory T cells. a. are obtained from a method comprising the steps of i. providing a sample derived from an isolated blood sample of said patient, ii. adding a photosensitizing agent to the sample, and subjecting the sample to irradiation.
21. Adiponectin and / or ARA for use in the treatment of a tumor patient according to claim 19 or 20, wherein the photosensitizing agent is 8-methoxypsoralen and / or the irradiation is UVA irradiation.