Monoclonal antibodies for CSPG4 for the diagnosis and treatment of basal breast carcinoma
It is disclosed herein that condroitin sulfate proteoglycan 4 (CSPG4), also known as high molecular weight melanoma associated antigen, is overexpressed on basal breast carcinoma cells (BBC), specifically triple negative basal breast carcinoma cells (TNBC). Methods for detecting basal breast cancer in a subject are disclosed. Methods are also disclosed for inhibiting the growth of a basal breast cancer cell. These methods include contacting the basal breast cancer cell with an effective amount of an antibody that specifically binds CSPG4. Additional treatment methods, and the use of antibody panels, are also described herein.
1. A method for treating a subject that has a triple negative basal breast cancer, comprising:
selecting the subject that has triple negative basal breast cancer; and
administering to the subject an effective amount of a pharmaceutical composition comprising an antibody or antigen binding fragment thereof that specifically binds chondroitin sulfate proteoglycan 4 (CSPG4),
thereby treating the triple negative basal breast cancer cell in the subject.
2. The method of claim 1 , wherein the antibody or antigen binding fragment thereof is covalently linked to an effector molecule.
3. The method of claim 1 , wherein the antibody is a monoclonal antibody.
4. The method of claim 1 , wherein treating the subject comprises reducing metastasis of the basal breast cancer cell in vivo.
5. The method of claim 2 , wherein the effector molecule is a chemotherapeutic agent.
6. The method of claim 2 , wherein the effector molecule comprises a toxic moiety.
7. The method of claim 6 , wherein the toxic moiety is selected from the group consisting of ricin A, abrin, diphtheria toxin or a subunit thereof, Pseudomonas exotoxin or a portion thereof, and botulinum toxins A through F.
8. The method of claim 7 , wherein the Pseudomonas exotoxin is selected from the group consisting of PE35, PE37, PE38, and PE40.
9. The method of claim 1 , wherein the subject has undergone surgical removal of a triple negative basal breast carcinoma primary tumor; and wherein inhibiting the growth of the basal breast cancer cell comprises preventing tumor recurrence in vivo.
10. The method of claim 1 , further comprising administering to the subject an additional chemotherapeutic agent.
11. The method of claim 10 , wherein the additional chemotherapeutic agent is a mitotic inhibitor, an alkylating agent, an anti-metabolite, an intercalating antibiotic, a growth factor inhibitor, a cell cycle inhibitor, an enzyme, a topoisomerase inhibitor, an anti-androgen, or an anti-angiogenesis agent.
12. The method of claim 1 , wherein the subject has metastatic triple negative basal breast cancer.