Methods of treating triple-negative breast cancer using compositions of antibodies and carrier proteins
Described herein are methods, formulations and kits for treating a patient with triple-negative breast cancer with nanoparticle complexes comprising a carrier protein (e.g., albumin), paclitaxel and a binding agent specific for a target antigen expressed by the cells (e.g., an anti-VEGF antibody).
1. A method for treating a breast cancer cell characterized as having a triple negative phenotype, comprising administering to the breast cancer cell a composition comprising a therapeutic amount of nanoparticle complexes, the complexes comprising: a) albumin; b) an effective amount of a binding agent having an antigen-binding portion that binds to a target antigen expressed by said cancer cells so as to provide directional guidance of the nanoparticle complexes to said cells; and c) an effective amount of paclitaxel.
2. A method for treating a patient afflicted with breast cancer characterized as having a triple negative phenotype and further characterized as expressing an antigen, said method comprises administering to the patient a therapeutic amount of nanoparticle complexes, said nanoparticle complexes comprising: a) albumin; b) an effective amount of a binding agent having an antigen-binding portion that binds to the antigen so as to provide directional guidance of the nanoparticle complexes to said cancer; and c) an effective amount of paclitaxel.
3. The method of claim 2 , wherein said binding agents are arranged on the outside surface of the nanoparticle complexes.
4. The method of claim 2 , wherein the binding agent is an antibody selected from an anti-VEGF antibody, an anti-cancer testis (CT) antigen antibody, an anti-folate receptor alpha (FR-alpha) antibody, an anti-programmed death-ligand 1 (PD-L1) antibody, an anti-programmed cell death protein 1 (PD-1) antibody, an anti-epidermal growth factor receptor (EGFR) antibody, an anti-C-kit antibody, and an anti-basal cytokeratin antibody.
5. The method of claim 2 , wherein the binding agent is an anti-VEGF antibody.
6. The method of claim 5 , wherein the anti-VEGF antibody is bevacizumab or a biosimilar version thereof.
7. The method of claim 4 , wherein the binding agent is an anti-CT antigen antibody.
8. The method of claim 7 , wherein the CT antigen is selected from TSAG10, a MAGE family member, NY-ESO-1/CTAG1B, CTAG2, PLAC1, and DKKL1.
9. The method of claim 8 , wherein the MAGEA family member is selected from MAGEA2B, MAGEA3, MAGEA4, MAGEA5, MAGEA6, MAGEA9, MAGEA 10, MAGEA12.
10. The method of claim 4 , wherein the binding agent is an anti-basal cytokeratin antibody.
11. The method of claim 10 , wherein the basal cytokeratin is CK-5, CK-14, or CK-17.
12. The method of claim 4 , wherein the binding agent is an anti-PD-L1 antibody.
13. The method of claim 12 , wherein the anti-PD-L1 antibody is BMS-936559, atezolizumab, durvalumab, or avelumab.
14. The method of claim 4 , wherein the binding agent is an anti-PD-1 antibody.
15. The method of claim 14 , wherein the anti-PD-1 antibody is nivolumab or pembrolizumab.
16. The method of claim 4 , wherein the anti-epidermal growth factor receptor (EGFR) antibody is cetuximab or panitumumab.
17. The method of claim 2 , wherein the antigen binding portion is an aptamer or a Fab fragment.
18. The method of claim 2 , wherein the breast cancer is resistant to conventional hormonal therapies and/or trastuzumab therapy.
19. The method of claim 2 , wherein the composition is administered in a dose that provides 75-175 mg/m2 of the paclitaxel to the patient.
20. The method of claim 2 , wherein the patient is pretreated with a subtherapeutic dose of the antibody prior to administration of the nanoparticle composition.
21. The method of claim 2 , wherein the albumin is human serum albumin.
22. The method of claim 2 , wherein each said nanoparticle comprises between 100 and 1,000 antibodies.
23. The method of claim 2 , wherein the binding agents are arranged into a substantially single layer of binding agents on all or part of the surface of the nanoparticle.
24. A method for treating a patient afflicted with breast cancer characterized as having a triple negative phenotype and further characterized as expressing VEGF, said method comprises treating said patient with a composition comprising a therapeutic amount of nanoparticle complexes, said nanoparticle complexes comprising: a) human serum albumin;
b) an effective amount of bevacizumab or a biosimilar version thereof so as to provide directional guidance of the nanoparticle complexes to said cells; and c) effective amount of paclitaxel.