IP Library › Granted Patent US 12,539,338
Granted Patent B2
US 12,539,338 · App. 17/823,044 · Granted Feb 3, 2026

Nano-enabled immunotherapy in cancer

Inventors: Andre E. Nel (Sherman Oaks, CA); Huan Meng (Los Angeles, CA); Kuo-Ching Mei (Los Angeles, CA)
Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
A61K47/6929A61K47/542A61K47/544A61K47/551A61K47/554A61K47/6905A61K47/6923B82Y5/00
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Quick Facts
Patent No.
US 12,539,338
App. No.
17/823,044
Granted
Feb 3, 2026
Kind
B2
Abstract

In certain embodiments a platform technology for the facilitating immune therapy in the treatment of cancer is provided. In certain embodiments nanocarriers are provided that facilitate delivery of an IDO inhibitor in conjunction with an inducer of cell death (ICD-inducer). In certain embodiments the IDO inhibitor is conjugated to a component of a lipid bilayer forming a nanovesicle. In still another embodiment, methods and compositions are provided where an ICD-inducing agent (e.g., doxorubicin, oxaliplatin, mitoxantrone etc.) and an IDO pathway inhibitor (e.g., an IDO inhibitor-prodrug) are integrated into a nanocarrier (e.g. a lipid-bilayer (LB)-coated nanoparticle), that allows systemic delivery to orthotopic pancreatic cancer site.

Claims (29)

1 . A nanovesicle drug carrier for the combined delivery of an IDO inhibitor and an inducer of immunogenic cell death (ICD), said nanovesicle drug carrier comprising:

a liposome comprising a lipid bilayer, wherein said lipid bilayer comprises cholesterol and cholesterol hemisuccinate (CHEMS), wherein the cholesterol is conjugated to the IDO inhibitor 1-methyl-D-tryptophan (indoximod); and

a cargo within said liposome where said cargo comprises an agent that induces immunogenic cell death (ICD) (ICD-inducer), wherein said agent is doxorubicin loaded on a cargo trapping agent.

2 . The nanovesicle drug carrier of claim 1 , wherein said lipid bilayer comprises:

a phospholipid; and

cholesterol conjugated to indoximod (Chol-IND).

3 . The nanovesicle drug carrier of claim 2 , wherein said phospholipid comprises:

a saturated fatty acid with a C14-C20 carbon chain, and/or an unsaturated fatty acid with a C14-C20 carbon chain, and/or a natural lipid comprising a mixture of fatty acids with C12-C20 carbon chains; and/or

a phospholipid selected from the group consisting of phosphatidylcholine (DPPC), 1,2-dimyristoleoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-sn-glycero-3-phospho-rac-glycerol (DSPG), 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG), distearoylphosphatidylcholine (DSPC), 1,2-dieicosenoyl-sn-glycero-3-phosphocholine, and diacylphosphatidylcholine (DAPC); or

a natural lipid selected from the group consisting of egg phosphatidylcholine (egg PC), and soy phosphatidylcholine (soy PC); and/or

distearoylphosphatidylcholine (DSPC).

4 . The nanovesicle drug carrier of claim 2 , wherein said lipid bilayer comprises an mPEG phospholipid with a phospholipid C14-C18 carbon chain, and a PEG molecular weight ranging from about 350 Da to 5000 Da.

5 . The nanovesicle drug carrier of claim 4 , wherein said lipid bilayer comprises 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG (DSPE-PEG).

6 . The nanovesicle drug carrier of claim 2 , wherein said lipid bilayer comprises DSPC:Chol-IND:DSPE-PEG or DPPG:Chol-IND:DSPE-PEG.

7 . The nanovesicle drug carrier of claim 6 , wherein:

the ratio of DSPC:Chol-IND:DSPE-PEG ranges from 40-90% DSPC: 10%-50% Chol-IND: 1%-10% DSPE-PEG molar ratio; or

the ratio of DSPC:Chol-IND:DSPE-PEG is about 50:40:5 molar ratio, the ratio of DPPG:Chol-IND:DSPE-PEG ranges from 40-90% DPPG: 10%-50% Chol-IND: 1%-10% DSPE-PEG molar ratio; or

the ratio of DPPG:Chol-IND:DSPE-PEG is about 50:40:5 molar ratio.

8 . The nanovesicle drug carrier of claim 2 , wherein said lipid bilayer further comprises a cholesterol derivative selected from the group consisting of lysine-based cholesterol (CHLYS), and PEGylated cholesterol (Chol-PEG).

9 . The nanovesicle drug carrier of claim 2 , wherein the IDO inhibitor conjugated to cholesterol comprises a compound having the structure:

10 . The nanovesicle drug carrier of claim 1 , wherein said cargo trapping agent before reaction with the cargo drug loaded in the vesicle, is selected from the group consisting of citric acid, triethylammonium sucrose octasulfate (TEA 8 SOS), (NH4) 2 SO 4 , an ammonium salt, a trimethylammonium salt, and a triethylammonium salt.

11 . The nanovesicle drug carrier of claim 1 , wherein said drug carrier is conjugated to a moiety selected from the group consisting of a targeting moiety, a fusogenic peptide, and a transport peptide.

12 . The nanovesicle drug carrier of claim 1 , wherein the IDO inhibitor and the ICD inducer are synergistic in their activity against a cancer.

13 . A pharmaceutical formulation comprising:

a nanovesicle drug carrier of claim 1 and a pharmaceutically acceptable carrier.

14 . A method of treating a colon, pancreatic or breast cancer, said method comprising:

administering to a subject in need thereof an effective amount of a nanovesicle drug carrier of claim 1 .

15 . A method of treating a colon, pancreatic or breast cancer in a mammal, said method comprising:

administering to an intra-tumoral or peri-tumoral site an effective amount of a nanovesicle drug carrier of claim 1 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 30, 2025
From: MEI, KUO-CHING; MENG, HUAN; NEL, ANDRE E.
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 072735/0745 →
Continuity (6)
Continuation 16687368 · Nov 18, 2019
Continuation In Part PCTUS2018033265 · May 17, 2018
Provisional Application 62914950 · Oct 14, 2019
Provisional Application 62614325 · Jan 5, 2018
Provisional Application 62507996 · May 18, 2017
Related Publication 20230241244A1 · Aug 3, 2023
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