Formulated and/or co-formulated liposome compositions containing toll-like receptor (“TLR”) agonist prodrugs useful in the treatment of cancer and methods thereof
Formulated and/or co-formulated liposomes comprising TLR prodrugs and/or TLR Lipid Moieties and methods of making the liposomes are disclosed herein. The TLR prodrug compositions comprise a drug moiety, a lipid moiety, and linkage unit that inhibit Toll-Like Receptor (e.g., TLR1/2, TLR4, and/or TLR7). The TLR 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. A Toll-like receptor (TLR) prodrug composition comprising TR3 as the TLR prodrug, TR3 having the following structure:
2. A nanocarrier comprising the TLR prodrug of claim 1 whereby the nanocarrier releases an active TLR inhibitor after cleavage of the linker unit joining the lipid moiety to the drug moiety.
3. The nanocarrier of claim 2 , whereby the nanocarrier is further co-formulated with an iNKT (i-Natural Killer T cell) activator.
4. The nanocarrier of claim 3 , wherein the iNKT activator is Alpha-galactosylceramide (α-GalCer).
5. The nanocarrier of claim 2 , whereby the nanocarrier is further co-formulated with an immune modulating agent, wherein the immune modulating agent is selected from the group consisting of other TLR agonists and/or prodrugs, immunogenic-cell death inducing chemotherapeutics, IDO (indoleamine 2,3-dioxygenase) antagonists, STING (stimulator of interferon genes protein) agonists, CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) and inhibitors, PD-1/PD-L1 (programmed cell death 1/programmed cell death ligand 1) inhibitors and/or prodrugs thereof.
6. The nanocarrier of claim 2 , whereby the nanocarrier is further co-formulated with an ICD (immunogenic cell death)-inducing chemotherapeutic, wherein the ICD-inducing chemotherapeutic is selected from the group consisting of Doxorubicin (DOX), Mitoxantrone (MTO), Oxaliplatin (OXA), Cyclophosphamide (CP), Bortezomib, Carfilzimib, or Paclitaxel.
7. The nanocarrier of claim 2 , further comprising doxorubicin (DOX).
8. The nanocarrier of claim 2 , wherein the nanocarrier comprises a liposome.
9. The nanocarrier of claim 2 , wherein the nanocarrier comprises a solid-lipid nanoparticle (SLNP).