Methods and compositions for car t cell therapy

Patent metadata

Field	Value
Publication number	US-2019091308-A1
Application number	US-201716092054-A
Country	US
Kind code	A1
Filing date	Apr 7, 2017
Priority date	Apr 8, 2016
Publication date	Mar 28, 2019
Grant date	—

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

1 . A method of treatment of a cancer, the method comprising
i) administering to a patient a first dose of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound comprises a small molecule ligand linked to a targeting moiety by a linker; ii) administering to the patient a CAR T cell composition wherein the CAR T cell comprises a CAR directed to the targeting moiety; ii) administering to the patient a second dose of the compound, or the pharmaceutically acceptable salt thereof, wherein the second dose is different than the first dose; and iv) treating the patient to ameliorate the cancer.

2 . A method of treatment of a cancer, the method comprising
i) administering to the patient a first conjugate, or a pharmaceutically acceptable salt thereof; ii) administering to the patient a CAR T cell composition wherein the CAR T cell comprises a CAR directed to the targeting moiety; iii) administering to the patient a second conjugate, or a pharmaceutically acceptable salt thereof, wherein the first and the second conjugate each comprise a small molecule ligand linked to a targeting moiety by a linker and wherein the first conjugate and the second conjugate are different; and iv) treating the patient to ameliorate the cancer.

3 . A method of treatment of a cancer, the method comprising
i) administering to a patient a first dose of a first conjugate, or a pharmaceutically acceptable salt thereof; ii) administering to the patient a CAR T cell composition wherein the CAR T cell comprises a CAR directed to the targeting moiety; ii) administering to the patient a second dose of a second conjugate, or a pharmaceutically acceptable salt thereof, wherein the first conjugate and the second conjugate each comprise a small molecule ligand linked to a targeting moiety, wherein the first conjugate and the second conjugate are different, and wherein the first dose and the second dose are different; and iv) treating the patient to ameliorate the cancer.

4 . The method of claim 2 wherein the linker in the first conjugate, or the pharmaceutically acceptable salt thereof, and the linker in the second conjugate, or the pharmaceutically acceptable salt thereof, are different.

5 . The method of claim 2 wherein the linker in the first conjugate, or the pharmaceutically acceptable salt thereof, and the linker in the second conjugate, or the pharmaceutically acceptable salt thereof, are the same.

6 . The method of claim 2 wherein the ligand in the first conjugate, or the pharmaceutically acceptable salt thereof, and the ligand in the second conjugate, or the pharmaceutically acceptable salt thereof, are different.

7 . The method of claim 2 wherein the ligand in the first conjugate, or the pharmaceutically acceptable salt thereof, and the ligand in the second conjugate, or the pharmaceutically acceptable salt thereof, are the same.

8 . The method of claim 2 wherein the targeting moiety in the first conjugate, or the pharmaceutically acceptable salt thereof, and the targeting moiety in the second conjugate, or the pharmaceutically acceptable salt thereof, are different.

9 . The method of claim 2 wherein the targeting moiety in the first conjugate, or the pharmaceutically acceptable salt thereof, and the targeting moiety in the second conjugate, or the pharmaceutically acceptable salt thereof, are the same.

10 . The method of claim 1 wherein the ligand is selected from a folate, DUPA, a CAIX ligand, an NK-1R ligand, a ligand of gamma glutamyl transpeptidase, and a CCK2R ligand.

11 . The method of claim 10 wherein the ligand is a folate.

12 . The method of claim 10 wherein the ligand is an NK-1R ligand.

13 . The method of claim 10 wherein the ligand is DUPA.

14 . The method of claim 10 wherein the ligand is a CCK2R ligand.

15 . The method of claim 10 wherein the ligand is a ligand of gamma glutamyl transpeptidase.

16 . The method of claim 1 wherein the targeting moiety is selected from 2,4-dinitrophenol (DNP), 2,4,6-trinitrophenol (TNP), biotin, digoxigenin, fluorescein, fluorescein isothiocyanate (FITC), NHS-fluorescein, pentafluorophenyl ester (PFP), tetrafluorophenyl ester (TFP), a knottin, a centyrin, and a DARPin.

17 . The method of claim 16 wherein the targeting moiety is FITC.

18 . The method of claim 16 wherein the targeting moiety is DNP.

19 . The method of claim 16 wherein the targeting moiety is TNP.

20 . The method of claim 1 wherein the linker comprises polyethylene glycol (PEG), polyproline, a hydrophilic amino acid, a sugar, an unnatural peptidoglycan, a polyvinylpyrrolidone, and/or pluronic F-127.

21 .- 72 . (canceled)

Assignees

• Purdue Research Foundation
• Endocyte Inc

Inventors

• Low Philip Stewart
• Chu Haiyan
• Lee Yong Gu

Classifications

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2319/02

  containing a signal sequence · CPC title

• A61K47/555

  pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells · CPC title

• C07K2319/03

  containing a transmembrane segment · CPC title