Diagnostic methods for t cell therapy

Patent metadata

Field	Value
Publication number	US-12559718-B2
Application number	US-202318455033-A
Country	US
Kind code	B2
Filing date	Aug 24, 2023
Priority date	May 28, 2015
Publication date	Feb 24, 2026
Grant date	Feb 24, 2026

Abstract

The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. The invention includes methods of identifying a patient who would respond well to a T cell therapy or conditioning a patient prior to a T cell therapy so that the patient responds well to a T cell therapy. The conditioning involves administering one or more preconditioning agents prior to a T cell therapy and identifying biomarker cytokines prior to administering a T cell therapy.

First claim

What is claimed is:

1 . A method for treating a leukemia in a subject with chimeric antigen receptor (CAR) T cell therapy comprising:
(i) administering to the subject one or more preconditioning agents that are capable of increasing a serum level of interleukin-15 (“IL-15”), interleukin-7 (“IL-7”), and any of monocyte chemotactic protein 1 (“MCP-1”), C-reactive protein (CRP), and interferon gamma-induced protein 10 (“IP-10”), wherein the preconditioning agents comprise cyclophosphamide and fludarabine; and (ii) administering a therapeutically effective amount of anti-CD19 CAR T cell therapy to the subject on day zero, wherein the subject is determined to exhibit an increase in the serum level at day zero prior to the administration of CAR T cell therapy of IL-15, and IL-7, and any of MCP-1, CRP, and IP-10, relative to their baseline serum levels prior to the administration of the preconditioning agents, wherein the IL-15, IL-7, MCP-1, CRP, and IP-10 serum levels are measured by an enzyme-linked immunosorbent assay (ELISA) or any method that detects the amount of protein in the serum for each protein and allows for their quantification, and wherein the serum level of IL-15 is increased by at least 5-fold.

2 . A method for identifying a subject as having an improved response to anti-CD19 CAR T cell therapy comprising (i) administering to the subject one or more preconditioning agents that are capable of increasing the serum level of IL-15 and IL-7, and any of MCP-1, CRP, and IP-10, wherein the preconditioning agents comprise cyclophosphamide and fludarabine; (ii) measuring the serum levels of IL-15, IL-7, and any of MCP-1, CRP, and IP-10 at baseline, which is prior to the administration of the preconditioning agent(s), and their serum levels at day zero, which is after administration of the preconditioning agent(s) and prior to, but on the day of, administration of CAR T cell therapy; wherein the IL-15, IL-7, and any of MCP-1, CRP, and IP-10 serum levels are measured by an enzyme-linked immunosorbent assay (ELISA) or any method that detects the amount of protein in the serum for each protein and allows for their quantification; and wherein the subject is identified as having an improved response to fer anti-CD19 CAR T cell therapy if there is an increase in the serum levels of IL-15 and IL-7, and any of MCP-1, CRP, and IP-10 at day zero, prior to the administration of CAR T cell therapy and relative to their baseline serum levels; and (ii) administering to the subject anti-CD19 CAR T cell therapy, wherein the subject has leukemia, and wherein the serum level of IL-15 is increased by at least 5-fold.

3 . A method for increasing a serum level of IL-15 and IL-7 and any of MCP-1, CRP, and IP-10 to pre-condition a subject in need of anti-CD19 CAR T cell therapy comprising administering to the subject one or more preconditioning agents, wherein the subject is treated with anti-CD19 CAR T cell therapy at day zero when exhibiting an increase in the serum level of IL-15 and IL-7, and any of MCP-1, CRP, and IP-10 prior to, but on the day of administration of the therapy, relative to baseline levels prior to pre-conditioning, wherein IL-15, IL-7, and any of MCP-1, CRP, and IP-10 serum levels are measured by an enzyme-linked immunosorbent assay (ELISA) or any method that detects the amount of protein in the serum for each protein and allows for their quantification; wherein the preconditioning agents comprise cyclophosphamide and fludarabine, wherein the subject has leukemia, and wherein the serum level of IL-15 is increased by at least 5-fold.

4 . The method of claim 1 , wherein:
(i) a dose of cyclophosphamide administered to the subject is from about 300 mg/m 2 /day to about 2000 mg/m 2 /day; (ii) a dose of fludarabine administered to the subject is from about 20 mg/m 2 /day to about 900 mg/m 2 /day; or (iii) both (i) and (ii).

5 . The method of claim 1 , wherein:
(i) a dose of cyclophosphamide administered to the subject is about 350 mg/m 2 /day, about 400 mg/m 2 /day, about 450 mg/m 2 /day, about 500 mg/m 2 /day, about 550 mg/m 2 /day, about 600 mg/m 2 /day, about 650 mg/m 2 /day, about 700 mg/m 2 /day, about 800 mg/m 2 /day, about 900 mg/m 2 /day, or about 1000 mg/m 2 /day; (ii) a dose of fludarabine administered to the subject is about 25 mg/m 2 /day, about 30 mg/m 2 /day, about 35 mg/m 2 /day, about 40 mg/m 2 /day, about 45 mg/m 2 /day, about 50 mg/m 2 /day, about 55 mg/m 2 /day, about 60 mg/m 2 /day, about 65 mg/m 2 /day, about 70 mg/m 2 /day, about 75 mg/m 2 /day, about 80 mg/m 2 /day, about 85 mg/m 2 /day, about 90 mg/m 2 /day, about 95 mg/m 2 /day, about 100 mg/m 2 /day, about 200 mg/m 2 /day, or about 300 mg/m 2 /day; or (iii) any combination thereof.

6 . The method of claim 1 , wherein a dose of cyclophosphamide administered to the subject is about 900 mg/m 2 /day to about 1000 mg/m 2 /day and a dose of fludarabine administered to the subject is about 25 mg/m 2 /day.

7 . The method of claim 1 , wherein a dose of cyclophosphamide is administered once for one day.

8 . The method of claim 1 , wherein a dose of fludarabine is administered daily for three days.

9 . The method of claim 1 , wherein the anti-CD19 CAR T cell therapy comprises administering engineered anti-CD19 CAR T cells at a dose of about 1×10 6 to about 5×10 6 engineered CAR T cells/kg.

10 . The method of claim 1 , wherein the leukemia is Acute Lymphoblastic Leukemia (ALL).

11 . The method of claim 1 , wherein the dose of cyclophosphamide administered to the subject is about 900 mg/m 2 /day for one day, and the dose of fludarabine administered to the subject is about 25 mg/m 2 /day for 3 days.

12 . The method of claim 2 , wherein:
(i) a dose of cyclophosphamide administered to the subject is from about 300 mg/m 2 /day to about 2000 mg/m 2 /day; (ii) a dose of fludarabine administered to the subject is from about 20 mg/m 2 /day to about 900 mg/m 2 /day; or (iii) both (i) and (ii).

13 . The method of claim 2 , wherein:
(i) a dose of cyclophosphamide administered to the subject is about 350 mg/m 2 /day, about 400 mg/m 2 /day, about 450 mg/m 2 /day, about 500 mg/m 2 /day, about 550 mg/m 2 /day, about 600 mg/m 2 /day, about 650 mg/m 2 /day, about 700 mg/m 2 /day, about 800 mg/m 2 /day, about 900 mg/m 2 /day, or about 1000 mg/m 2 /day; (ii) a dose of fludarabine administered to the subject is about 25 mg/m 2 /day, about 30 mg/m 2 /day, about 35 mg/m 2 /day, about 40 mg/m 2 /day, about 45 mg/m 2 /day, about 50 mg/m 2 /day, about 55 mg/m 2 /day, about 60 mg/m 2 /day, about 65 mg/m 2 /day, about 70 mg/m 2 /day, about 75 mg/m 2 /day, about 80 mg/m 2 /day, about 85 mg/m 2 /day, about 90 mg/m 2 /day, about 95 mg/m 2 /day, about 100 mg/m 2 /day, about 200 mg/m 2 /day, or about 300 mg/m 2 /day; or (iii) any combination thereof.

14 . The method of claim 2 , wherein a dose of cyclophosphamide administered to the subject is about 900 mg/m 2 /day to about 1000 mg/m 2 /day and a dose of fludarabine administered to the subject is about 25 mg/m 2 /day.

15 . The method of claim 2 , wherein a dose of cyclophosphamide is administered once for one day.

16 . The method of claim 2 , wherein a dose of fludarabine is administered daily for three days.

17 . The method of claim 2 , wherein the anti-CD19 CAR T cell therapy comprises administering engineered anti-CD19 CAR T cells at a dose of about 1×10 6 to about 5×10 6 engineered CAR T cells/kg.

18 . The method of claim 2 , wherein the leukemia is Acute Lymphoblastic Leukemia (ALL).

19 . The method of claim 2 , w

Assignees

• Kite Pharma Inc
• Usa As Represented By The Sec Dept Of Hhs

Inventors

• Bot Adrian
• Wiezorek Jeffrey S
• GO William
• JAIN Rajul
• Kochenderfer James N
• Rosenberg Steven A

Classifications

• C12N15/85

  for animal cells · CPC title

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/665

  having oxygen as a ring hetero atom, e.g. fosfomycin · CPC title

• A61K31/52

  Purines, e.g. adenine · CPC title