Use of Pegylated IL-10 to Treat Cancer

Abstract

Provided are methods of treatment for tumors. In particular, methods are provided for use of a chemically modified IL-10 to treat tumors.

Description

[0001] This application is a utility patent application which claims benefit of U.S. Provisional patent application 60 / 915,603, filed May 2, 2007 and 60 / 848,326, filed Sep. 28, 2006, both of which are hereby incorporated by reference.FIELD OF THE INVENTION [0002] The present invention concerns uses of mammalian cytokine molecules and related reagents. More specifically, the invention relates to identification of chemically modified mammalian cytokine proteins that can be used in the treatment of proliferative disorders. BACKGROUND OF THE INVENTION [0003] Cancers and tumors can be controlled or eradicated by the immune system. The immune system includes several types of lymphoid and myeloid cells, e.g., monocytes, macrophages, dendritic cells (DCs), eosinophils, T cells, B cells, and neutrophils. These lymphoid and myeloid cells produce secreted signaling proteins known as cytokines. The cytokines include, e.g., interleukin-10 (IL-10), interferon-gamma (IFNγ), IL-12, and IL-23. Immun...

AI Technical Summary

Benefits of technology

[0007] The present invention is based upon the discovery that pegylated IL-10 is an improved modulator of tumor growth.

[0008] The present invention provides method of inhibiting or reducing growth of a tumor or cancer comprising contacting the tumor with an effective amount of a pegylated interleukin-10 (PEG-IL-10). In one embodiment, the PEG-IL-10 is mono-PEG-IL-10. The PEG-IL-10 comprises an SC-PEG-12K linker. In an alternative embodiments the PEG-IL-10 comprises a methoxy-PEG-aldehyde (PALD-PEG) linker. In certain embodiments the PALD-PEG linker comprises a PEG molecule having a molecular weight selected from the group consisting 5 KDa, 12 KDa, or 20 KDa. The PEG-IL-10 inhibits growth of the tumor or cancer or the PEG-IL-10 reduces the size of the tumor or cancer. The PEG-IL-10 increases infiltration of CD8+ T cells into the tumor when compared to non-pegylated IL-10. In another embodiment, PEG-IL-10 increases the expression of at least one inflammatory cytokine, which can be selected from the group consisting of IFNγ, IL-4, IL-6, IL-10, and RANK-ligand (RANK-L). In certain embodiements, the PEG-IL-10 is co-administered with at least one chemotherapeutic agent. The chemotherapeutic agent can be at least one of the chemotherapeutic agents of Table 16. In certain embodiments, the the tumor or cancer is selected from the group consisting of colon cancer, ovarian cancer, breast cancer, melanoma, lung cancer, glioblastoma, and leukemia.

Problems solved by technology

Excessive immune response can produce pathological consequences, such as autoimmune disorders, whereas impaired immune response may result in cancer.

Unfortunately, the serum half life for IL-10 is relatively short, i.e., 2-6 hours (see, e.g., Smith et al.