Granted Patent B2

US 12,491,248 · App. 17/787,836 · Granted Dec 9, 2025

Inventors: Robert Zeiser (Freiburg, DE); Petya Apostolova (Freiburg, DE); Justus Duyster (Freiburg, DE)

A61K41/0066A61K40/11A61K40/15A61K40/22A61K40/416A61P37/00C12N5/0646A61K2239/31A61K2239/38C12N2529/10

Abstract

Claims (26)

1 . A method comprising the steps of:

providing a sample derived from a blood sample of a subject that (i) suffers from cancer, (ii) is concurrently receiving an immunosuppressive drug and/or is refractory to immunosuppressive drugs, (iii) is receiving a checkpoint-inhibitor therapy, and (iv) is suspected of developing or has developed symptoms of immune-related adverse events (irAE) comprising autoimmune colitis;

adding a photosensitizing agent to the sample;

subjecting the sample to irradiation to generate or induce the formation of immunoregulatory NK cells in the sample; and

administering the NK cells to the subject while checkpoint-inhibitor therapy is ongoing,

wherein the NK cells are autologous with respect to the subject.

2 . The method according to claim 1 , wherein the photosensitizing agent is 8-methoxypsoralen and/or the irradiation is UVA irradiation.

3 . The method according to claim 1 , wherein the subject shows symptoms of or suffers from irAE.

4 . The method according to claim 1 , wherein the cancer is a malignant melanoma or another cancer treatable by checkpoint-inhibitor therapy.

5 . The method according to claim 1 , wherein the subject is concurrently receiving an immunosuppressive drug, and the immunosuppressive drug is selected from the group consisting of a steroid, a corticosteroid, a cyclosporine an anti-TNF antibody, and combinations thereof.

6 . The method according to claim 5 , wherein the anti-TNF antibody is infliximab.

7 . The method according to claim 1 , wherein the checkpoint-inhibitor therapy comprises administration of at least one of anti-CTLA4 antibodies and anti-PD-1 antibodies.

8 . A method for treating a subject in need thereof that is receiving or has received a checkpoint-inhibitor therapy and shows symptoms of or suffers from irAE comprising autoimmune colitis, comprising:

subjecting the subject in need thereof to extracorporeal photopheresis therapy (ECP).

9 . The method according to claim 8 , wherein ECP comprises collecting a sample derived from a blood sample of the subject in need thereof.

10 . The method according to claim 9 , wherein ECP further comprises adding a photosensitizing agent to the sample.

11 . The method according to claim 10 , wherein ECP further comprises subjecting the sample to irradiation.

12 . The method according to claim 11 , wherein adding the photosensitizing agent to the sample and subjecting the sample to irradiation generates or induces the formation of immunoregulatory NK cells in the sample.

13 . The method according to claim 12 , wherein the irradiation is UVA irradiation.

14 . The method according to claim 10 , wherein the photosensitizing agent is 8-methoxypsoralen.

15 . The method according to claim 8 , wherein the subject in need thereof suffers from malignant melanoma or another cancer treatable by checkpoint-inhibitor therapy.

16 . The method according to claim 8 , wherein the checkpoint-inhibitor therapy was discontinued after symptoms of irAE occurred in the subject.

17 . The method according to claim 8 , wherein symptoms of irAE occurred after the checkpoint-inhibitor therapy was discontinued.

18 . The method according to claim 8 , wherein symptoms of irAE were maintained after the checkpoint-inhibitor therapy was discontinued.

19 . The method according to claim 8 , wherein the subject is concurrently receiving an immunosuppressive drug and/or is refractory to immunosuppressive drugs.

20 . The method according to claim 19 , wherein the immunosuppressive drug is selected from the group consisting of a steroid, a corticosteroid, a cyclosporine, an anti-TNF antibody, and combinations thereof.

Assignments (14)

Priority Claims (1)

Continuity (1)

References Cited (92)