Albumin-CTLA-4 paclitaxel nanopartilce complex compositions and methods of making and using the same
Described herein are compositions of antibodies and carrier proteins and methods of making and using the same, in particular, as a cancer therapeutic. Also described are lyophilized compositions of antibodies and carrier proteins and methods of making and using the same, in particular, as a cancer therapeutic.
1. A lyophilized composition comprising nanoparticle complexes comprising
albumin;
antibodies, each having a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)-binding portion; and
paclitaxel;
said nanoparticle complexes being lyophilized, wherein upon reconstitution with an aqueous solution the nanoparticle complexes have binding specificity for CTLA-4 expressed by a cancer cell in vivo, wherein said complexes have an average size of less than 1 μm, and wherein the antibodies are associated with the albumin through non-covalent bonds.
2. The lyophilized composition of claim 1 that is stable at about 20° C. to about 25° C. for at least 3 months.
3. The lyophilized composition of claim 1 , wherein each of the nanoparticle complexes comprises between about 400 and about 800 antibodies.
4. The lyophilized composition of claim 1 , wherein less than 0.01% of nanoparticle complexes have a size greater than 800 nm.
5. The lyophilized composition of claim 1 , wherein said nanoparticle complexes have an average size of about 160 nm.
6. The lyophilized composition of claim 1 , wherein the albumin is human serum albumin.
7. The lyophilized composition of claim 1 , wherein the nanoparticle complexes have a dissociation constant between about 1×10 −11 M and about 1×10 −9 M.
8. The lyophilized composition of claim 1 which does not contain a bulking agent.
9. The lyophilized composition of claim 1 , wherein said nanoparticle complexes have an average size between about 130 nm and about 800 nm.
10. The lyophilized composition of claim 1 , wherein the ratio of albumin-paclitaxel nanoparticle to antibodies is between 10:1 and 10:30.
11. The lyophilized composition of claim 1 , wherein the ratio of albumin-paclitaxel nanoparticle to antibodies is between 10:2 and 10:6.
12. The lyophilized composition of claim 1 , wherein the antibodies are ipilimumab.
13. The lyophilized composition of claim 12 , wherein less than 0.01% of nanoparticle complexes have a size greater than 800 nm.
14. The lyophilized composition of claim 12 , wherein said nanoparticle complexes have an average size between about 130 nm and about 800 nm.
15. The lyophilized composition of claim 12 , wherein the ratio of albumin-paclitaxel nanoparticle to antibodies is between 10:1 and 10:30.
16. The lyophilized composition of claim 12 , wherein the ratio of albumin-paclitaxel nanoparticle to antibodies is between 10:2 and 10:6.
17. The lyophilized composition of claim 1 , wherein each of the nanoparticle complexes comprises between about 100 and about 1000 antibodies.
18. The lyophilized composition of claim 1 , further comprising at least one additional cancer therapeutic agent.
19. The lyophilized composition of claim 1 , wherein the paclitaxel is associated with the albumin through non-covalent bonds.
20. The lyophilized composition of claim 12 , wherein the paclitaxel is associated with the albumin through non-covalent bonds.
21. A method for treating cancer in a subject in need thereof, the method comprising reconstituting a lyophilized nanoparticle composition in a pharmaceutically acceptable excipient to form a reconstituted nanoparticle composition and administering a therapeutically effective amount of the reconstituted nanoparticle composition to the subject, wherein the lyophilized composition comprises lyophilized nanoparticle complexes comprising albumin, antibodies having a CTLA-4-binding portion, and paclitaxel, wherein the cancer expresses CTLA-4 and upon reconstitution with the pharmaceutically acceptable excipient the nanoparticle complexes have binding specificity for CTLA-4 expressed by the cancer, wherein said complexes have an average size of less than 1 μm, and wherein the antibodies are associated with the albumin through non-covalent bonds.
22. A method of making a lyophilized nanoparticle composition comprising nanoparticle complexes comprising albumin, antibodies having a CTLA-4-binding portion, and paclitaxel, the method comprising mixing aqueous albumin-paclitaxel nanoparticles with the antibodies in vitro under conditions to form the nanoparticle complexes, and lyophilizing the nanoparticle complexes to form the lyophilized nanoparticle composition, such that when reconstituted with an aqueous solution the nanoparticle complexes have binding specificity for CTLA-4, wherein said complexes have an average size of less than 1 μm, wherein the antibodies are associated with the albumin through non-covalent bonds.