Methods of increasing delivery of anti-cancer agents to targets
The present invention provides compositions and methods for increasing the permeability of a stroma around a neoplasm, and particularly to cancer cells associated with solid tumors. In one embodiment, combining a therapeutic IgE antibody with an anti-cancer agent in accordance with the invention increases the delivery of the anticancer agent to the site of, for example, a solid tumor in a subject. In one embodiment, combining a therapeutic IgE antibody with an anti-cancer agent in accordance with the invention potentiates a tumor's responsiveness and sensitivity to the anti-cancer agent.
1. A method of treating a solid tumor, comprising administering to a subject in need thereof:
(a) a therapeutically effective amount of an IgE monoclonal antibody specific to MUC1 having a heavy chain variable region encoded by SEQ ID NO:1 and a light chain variable region encoded by SEQ ID NO:2;
(b) gemcitabine;
(c) a poly (I:C);
(d) an anti-PD-L1 antibody;
wherein the IgE monoclonal antibody is administered at least 30 minutes to 4 hours prior to administration of the gemcitabine;
wherein the poly (I:C) is first administered after first administration of the IgE monoclonal antibody and the gemcitabine;
wherein the poly (I:C) is administered 6 hours to 48 hours after administration of the gemcitabine; and
wherein the anti-PD-L1 antibody is first administered 6 hours to 48 hours after first administration of the poly (I:C).
2. The method of claim 1 , wherein the IgE monoclonal antibody is specific to MUC1 associated with the solid tumor's microenvironment.
3. The method of claim 1 , wherein the solid tumor's is pancreatic cancer, gastric cancer, colorectal cancer, ovarian cancer, breast cancer, or lung cancer.
4. The method of claim 1 ,
wherein the poly (I:C) is administered to the subject every second day.
5. The method of claim 4 ,
wherein the anti-PD-L1 antibody is administered to the subject alternatingly every second and third day.
6. The method of claim 1 , further comprising performing the method one additional time.
7. The method of claim 1 , further comprising performing the method two additional times.
8. The method of claim 1 , wherein the poly (I:C) is administered to the subject every fifth day; and the anti-PD-L1 antibody is administered to the subject alternatingly every second and third day.