Formulated and/or co-formulated liposome compositions containing IDO antagonist prodrugs useful in the treatment of cancer and methods thereof
Formulated and/or co-formulated liposomes comprising IDO prodrugs and methods of making the liposomes are disclosed herein. The IDO prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit that inhibit IDO-1. The IDO prodrugs can be formulated and/or co-formulated into a liposome to provide a method of treating cancer, immunological disorders, and other disease by utilizing a targeted drug delivery vehicle.
1. An IDO prodrug composition comprising an IDO prodrug having the following chemical structure:
2. A lipid nanoparticle (LNP) comprising, an IDO prodrug composition, wherein the IDO prodrug composition has the following chemical structure:
3. The lipid nanoparticle of claim 2 , wherein the Zav size is between 70 nm and 90 nm, and wherein the PDI of the liposome is between 0.001 and 0.250.
4. The lipid nanoparticle of claim 2 , further comprising α-galactosylceramide (α-GalCer).
5. The lipid nanoparticle of claim 2 , further comprising Telratolimod.
6. The lipid nanoparticle of claim 5 , further comprising an A2a receptor inhibitor.
7. The lipid nanoparticle of claim 2 , further comprising an A2a receptor inhibitor.
8. The lipid nanoparticle of claim 2 , further comprising Mitoxantrone (MTO).
9. The lipid nanoparticle of claim 2 , whereby the lipid nanoparticle is further co-formulated with an immune modulating agent, wherein the immune modulating agent is selected from the group consisting of immunogenic-cell death inducing chemotherapeutics, toll-receptor agonists, STING agonists, CTLA-4 inhibitors, or PD-1/PD-L1 inhibitors.
10. The lipid nanoparticle of claim 2 , whereby the lipid nanoparticle is further co-formulated with an Immunogenic Cell Death inducing chemotherapeutic, wherein the Immunogenic Cell Death inducing chemotherapeutic is selected from the group consisting of doxorubicin (DOX), mitoxantrone (MTO), oxaliplatin (OXA), cyclophosphamide (CP), Bortezomib, Carfilzomib, or Paclitaxel.
11. The lipid nanoparticle of claim 2 , further comprising doxorubicin (DOX).
12. The lipid nanoparticle of claim 2 , further comprising mitoxantrone (MTO).
13. The lipid nanoparticle of claim 10 , further comprising doxorubicin (DOX).
14. The lipid nanoparticle of claim 10 , further comprising mitoxantrone (MTO).
15. A method of treating a subject suffering or diagnosed with cancer comprising,
(i) administering to a subject an effective amount of a lipid nanoparticle, wherein the lipid nanoparticle comprises an IDO prodrug composition having the following chemical structure:
and
ii) a pharmaceutically acceptable salt.
16. The method of claim 15 , wherein the cancer is melanoma.
17. The method of claim 15 , wherein the cancer is colon cancer.
18. A kit comprising the IDO prodrug composition of claim 1 .
19. A kit comprising the lipid nanoparticle of claim 2 .