Use of Cytokine IP-10 as an Anti-Tumor Agent
Summary The invention provides compositions and methods for the diagnosis and treatment of both malignant and benign cell-proliferative diseases. When complexed to its receptor, IP-10 interacts with known cytokines, including FGF and TGFb; this interaction down-regulates cell division and/or results in T cell chemotaxis toward the sites of IP-10 localization. Uncontrolled cell proliferation is the hallmark of both cancer and non-neoplastic endothelial tissue disease. Local administration of IP-10 to model animals at sites of tumor formation or induction has been proven effective against neoplastic cell growth. IP-10 additionally inhibits non-neoplastic cell growth (e.g., as observed in arteriosclerosis, proliferative retinal disorders, hemangioma, cheloids, fibrosis and which accompanies inflammation). IP-10 may be administered as a protein, nucleic acid expression construct or cell that produces and secretes the IP-10 protein. Diagnostic testing for reduced IP-10 levels permits early intervention in proliferative disease, and IP-10 provides a useful drug screening target.
Luster, A.D. and P. Leder, 1995, "The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 5 and inhibits endothelial cell proliferation", J. Exp. Med., 182(1): 219-231.
Luster, A.D. and P. Leder, 1993, "IP-10, a -C-X-C- chemokine elicits a potent thymus-dependent antitumor response in vivo", J. Exp. Med., 178(3): 1057-1058.
Confirming reports of IP-10 anticancer efficacy:
Sgadari et al., 1996, "Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo", Proc. Natl. Acad. Sci. U.S.A., 93: 13791-13796.
Angiolillo et al., 1996, "A role for the interferon-inducible protein 10 in inhibition of angiogenesis by interleukin-12", Ann. N.Y. Acad. Sci., 795: 158-167.
Arenberg et al., 1996, "Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases", J. Exp. Med., 184(3): 981-992.
Applications Cancer therapeutic.
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