Compositions and methods for CAR T cell therapy

Patent metadata

Field	Value
Publication number	US-11759480-B2
Application number	US-202016921400-A
Country	US
Kind code	B2
Filing date	Jul 6, 2020
Priority date	Feb 28, 2017
Publication date	Sep 19, 2023
Grant date	Sep 19, 2023

Abstract

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

First claim

What is claimed is:

1. A method of treating a patient for cancer, the method comprising:
i) administering to the patient an amount of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a folate linked to fluorescein isothiocyanate (FITC);
ii) administering to the patient a chimeric antigen receptor T cell (CAR T cell) composition comprising CAR T cells comprising a polypeptide having the sequence set forth in SEQ ID NO: 2; and
iii) reducing or preventing cytokine release syndrome (CRS) or cytokine storm by administering to the patient an amount of a rescue agent comprising fluoresceinamine, FITC, or fluorescein, or a salted form thereof,
wherein the amount of the rescue agent is in molar excess relative to the amount of the compound and the molar excess is less than 100-fold molar excess relative to the amount of the compound;
whereupon the patient is treated for cancer.

2. The method of claim 1 , wherein the cancer is a folate receptor-expressing cancer.

3. The method of claim 1 , wherein the CAR has a recognition region and the recognition region is a single chain fragment variable (scFv) region of an anti-FITC antibody, wherein the CAR has a co-stimulation domain and the co-stimulation domain is CD137 (4-1BB), and wherein the CAR has an activation signaling domain and the activation signaling domain is a T cell CD3ζ chain.

4. The method of claim 1 , wherein the compound, or the pharmaceutically acceptable salt thereof, is not an antibody, and does not comprise a fragment of an antibody.

5. The method of claim 1 , wherein iii) comprises administering to the patient sodium fluorescein.

6. The method of claim 5 , wherein, prior to (iii), the patient shows signs of CRS or cytokine storm, and (iii) reduces CRS or cytokine storm.

7. The method of claim 6 , which further comprises determining a CRS grade in the patient and, when the CRS grade is 1, 2, 3 or 4, administering the amount of the rescue agent.

8. The method of claim 1 , wherein, prior to (iii), the patient shows signs of CRS or cytokine storm, and (iii) reduces CRS or cytokine storm.

9. The method of claim 8 , which further comprises determining a CRS grade in the patient and, when the CRS grade is 1, 2, 3 or 4, administering the amount of the rescue agent.

10. The method of claim 1 , wherein the method results in a decrease in tumor volume in the patient.

Assignees

• Endocyte Inc
• Purdue Research Foundation

Inventors

• Low Philip Stewart
• Chu Haiyan
• Lee Yong Gu
• Lu Yingjuan J
• Leamon Christopher Paul
• Wheeler Ii Leroy W

Classifications

• A61K40/4276

  Prostate specific membrane antigen [PSMA] · CPC title

• A61K40/4202

  Receptors, cell surface antigens or cell surface determinants · CPC title

• A61K40/429

  Small organic molecules e.g. cocaine or nicotine · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title