Compositions comprising GRIM-19 therapeutics and methods of use
The present invention provides nucleic acids encoding a fusion protein comprising a nucleotide sequence encoding GRIM-19 or a biologically active fragment or derivative thereof and a nucleotide sequence encoding a protein transduction domain. Proteins encoded by the nucleic acids, pharmaceutical compositions and methods of treatment are also provided. The invention also provides viral vectors comprising GRIM-19 or a biologically active fragment or derivative thereof, pharmaceutical compositions and methods of treatment using the same.
1. A method of treating a GRIM-19 negative cancer in a subject, comprising:
obtaining the results of an assay that measures the expression level in cancer tissue of one or more of CCL-5, CCL-22, CXCL-1, CXCL-2, CXCL-3, CXCL-4, CXCL-5, CXCL-7, CXCL-9, CXCL-10, CXCL-11, CXCL-12, CXCL-13, CXCL-14, CXCL-15, CXCL-16, CXCL-17, CX3CL1, CXCR-2, CXCR-3, CXCR-5, CXCR-6, CXCR-7, IL5, IL17B, IL-12B, TNFS14 (Light), EGFR, Fyn, MMP-7, MMP-19, MMP-20, MMP-23, MMP-24, CCL-2, CCL-14, CCL-15, CCR-4, CCR-7, CCR-9, CXCR-4, IL-1 and IL-36;
wherein positive responsiveness of the subject to the treatment is predicted when one or more of the CCL-5, the CCL-22, the CXCL-1, the CXCL-2, the CXCL-3, the CXCL-4, the CXCL-5, the CXCL-7, the CXCL-9, the CXCL-10, the CXCL-11, the CXCL-12, the CXCL-13, the CXCL-14, the CXCL-15, the CXCL-16, the CXCL-17, the CX3CL1, the CXCR-2, the CXCR-3, the CXCR-5, the CXCR-6, the CXCR-7, the IL5, the IL17B, the IL-12B, the TNFS14 (Light), the EGFR, the Fyn, the MMP-7, the MMP-19, the MMP-20, the MMP-23 and the MMP-24 is upregulated in the cancer tissue and/or one or more of the CCL-2, the CCL-14, the CCL-15, the CCR-4, the CCR-7, the CCR-9, the CXCR4, the IL-1 and the IL-36 is downregulated in the cancer tissue as measured in the assay, relative to non-cancerous correlative tissue,
wherein the treatment comprises directly administering to the cancer tissue a pharmaceutical composition comprising a fusion protein comprising GRIM-19 protein with an amino acid sequence of SEQ ID NO:11 or a derivative thereof having at least 99% identity to SEQ ID NO:11, linked to a protein transduction domain.
2. The method of claim 1 , wherein the cancer is selected from the group consisting of head and neck cancer, oral cancer and prostate cancer.
3. The method of claim 1 , wherein the subject is administered the composition in combination with at least one of one or more additional cancer therapeutics and radiotherapy.