COMBINATION CANCER IMMUNOTHERAPIES WITH ARGININE DEPLETION AGENTS
Provided are arginine depletion agents such as ADI-PEG for use in combination with cancer immunotherapies, for example, immune checkpoint modulators and T-cell adoptive immunotherapies. for treating various cancers. Also provided are related methods, compositions, patient care kits, and cell cultures.
1 . An use of an arginine deprivation agent of manufacturing a medicament for enhancing effector T-cells (Teff cells) activation.
2 . The use of claim 1 , wherein the effector T cells (Teff cells) express CD3 + marker and CD4 + marker.
3 . The use of claim 2 , wherein the effector T cells (Teff cells) express CD69 + marker.
4 . The use of claim 1 , wherein the effector T cells (Teff cells) express CD3 + marker and CD8 + marker.
5 . The use of claim 4 , wherein the effector T cells (Teff cells) express CD69 + marker.
6 . The use of claim 3 , wherein the effector T cells (Teff cells) further comprise CD274 + marker, CD279 + marker, or CD152 + marker.
7 . The use of claim 1 , wherein the arginine deprivation agent is an arginine deiminase (ADI) polypeptide.
8 . The use of claim 7 , wherein the ADI polypeptide comprises an amino acid sequence set forth in any one of SEQ ID NOs: 1 to 56.
9 . The use of claim 7 , wherein the ADI polypeptide is covalently bonded via a biocompatible linker to a number of PEG molecules.
10 . The use of claim 9 , wherein the ADI polypeptide is covalently bonded to more than one PEG molecule.
11 . The use of claim 10 , wherein the PEG molecules are straight chain PEG molecules or branch chain PEG molecules.
12 . The use of claim 10 , wherein the at least one PEG has a total weight average molecular weight of from about 10,000 Daltons to about 40,000 Daltons.
13 . The use of claim 12 , wherein the biocompatible linker comprises a succinyl group, an amide group, an imide group, a carbamate group, an ester group, an epoxy group, a carboxyl group, a hydroxyl group, a carbohydrate, a tyrosine group, a cysteine group, a histidine group, a methylene group, or a combination thereof.
14 . The use of claim 13 , wherein the source of the succinyl group is succinimidyl succinate.
15 . The use of claim 7 , wherein the arginine deprivation agent is pegylated arginine deiminase (ADI-PEG).
16 . The use of claim 15 , wherein the ADI-PEG is ADI-PEG 20.
17 . An use of an arginine deprivation agent of manufacturing a medicament for suppressing regulatory T-cells (Treg cells) activation.
18 . The use of claim 17 , wherein the regulatory T cells (Treg cells) express CD3 + marker, CD4 + marker, and CD25 + marker.
19 . The use of claim 18 , wherein the regulatory T cells (Treg cells) further comprise FoxP3 + marker, CD127 + marker, CD274 + marker, CD279 + marker, or CD152 + marker.
20 . The use of claim 17 , wherein the arginine deprivation agent is an arginine deiminase (ADI) polypeptide.
21 . The use of claim 20 , wherein the ADI polypeptide comprises an amino acid sequence set forth in any one of SEQ ID NOs: 1 to 56.
22 . The use of claim 20 , wherein the ADI polypeptide is covalently bonded via a biocompatible linker to a number of PEG molecules.
23 . The use of claim 22 , wherein the ADI polypeptide is covalently bonded to more than one PEG molecule.
24 . The use of claim 23 , wherein the PEG molecules are straight chain PEG molecules or branch chain PEG molecules.
25 . The use of claim 23 , wherein the at least one PEG has a total weight average molecular weight of from about 1,000 Daltons to about 40,000 Daltons.
26 . The use of claim 25 , wherein the biocompatible linker comprises a succinyl group, an amide group, an imide group, a carbamate group, an ester group, an epoxy group, a carboxyl group, a hydroxyl group, a carbohydrate, a tyrosine group, a cysteine group, a histidine group, a methylene group, or a combination thereof.
27 . The use of claim 26 , wherein the source of the succinyl group is succinimidyl succinate.
28 . The use of claim 20 , wherein the arginine deprivation agent is pegylated arginine deiminase (ADI-PEG).
29 . The use of claim 28 , wherein the ADI-PEG is ADI-PEG 20.