DNA cytokine vaccines and use of same for protective immunity against multiple sclerosis

Abstract

A method for treating a mammal for inducing protective immunity against an autoimmune disease including the step of administering to the mammal a therapeutic composition including a recombinant construct including an isolated nucleic acid sequence encoding a cytokine, the nucleic acid sequence being operatively linked to one or more transcription control sequences. A method for treating a mammal for inducing protective immunity against an autoimmune disease including the steps of (a) removing cells of the mammal; (b) transducing the cells in vitro with a recombinant construct including an isolated nucleic acid sequence encoding a cytokine, the nucleic acid sequence being operatively linked to one or more transcription control sequences; and (c) reintroducing the transduced cells to the mammal. A pharmaceutical composition including (a) a recombinant construct including an isolated nucleic acid sequence encoding a cytokine, the nucleic acid sequence being operatively linked to one or more transcription control sequences; and (b) a pharmaceutically acceptable carrier. And an antibody raised against a cytokine expressed by cells transduced with a recombinant construct including an isolated nucleic acid sequence encoding the cytokine, the nucleic acid sequence being operatively linked to one or more transcription control sequences.

Description

[0001] This is a Divisioal of U.S. patent application Ser. No. 09 / 123,485, filed Jul. 28, 1998.FIELD AND BACKGROUND OF THE INVENTION[0002] The present invention relates to DNA vaccines and DNA vaccination, and more particularly, to DNA encoding cytokines and the use of same as DNA vaccines for inducing protective immunity against autoimmune diseases. Most particularly, the present invention relates to DNA encoding C-C chemokines and tumor necrosis factor alpha and the use of same for protective immunity against multiple sclerosis.[0003] Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease of the central nervous system (CNS) which, for many years and for a variety of experimental protocols, serves as a model for the human disease, multiple sclerosis (MS), a chronic degenerative disease marked by patchy destruction of the myelin that surrounds and insulates nerve fibers and mild to severe neural and muscular impairments, since in both diseases circulating leukocyte...

AI Technical Summary

Problems solved by technology

A major disadvantage in treating chronic diseases with xenogenic neutralizing antibodies lies in their immunogenicity.

As already mentioned in the Background section hereinabove, a major disadvantage in treating chronic diseases with xenogenic neutralizing antibodies lies in their immunogenicity.

The underlying mechanism by which the immune system distinguishes a gene products transcribed at a privileged autoimmune site from the same gene product transcribed at a local site of inflammation is, however elusive.

The `natural` anti self production to TNF-.alpha. in EAE susceptible rats was, however, not sufficient to prevent the development of an autoimmune condition (6 / 6 sick rats).

As already mentioned, from a clinical perspective, however, a major disadvantage in treating chronic diseases with xenogenic neutralizing antibodies lies in their immunogenicity.

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