Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Reexamination Certificate
1998-02-24
2001-12-04
Saunders, David (Department: 1644)
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
C424S093200, C424S093700, C424S185100, C514S002600, C530S325000, C530S326000, C530S327000, C530S328000, C530S329000, C530S330000, C530S331000, C530S350000
Reexamination Certificate
active
06326465
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
This invention is related to the field of immunology. More particularly it is related to the field of modulation of immune responses, in particular induction of anti-tumor immune responses.
BACKGROUND OF THE INVENTION
Recent studies in man and in rat show that the administration of Cyclosporine (CsA) after autologous or syngeneic BMT induces an autoimmune syndrome resembling graft-vs-host disease (GVHD).
1-5
This syndrome is termed syngeneic or autologous GVHD. Results from animal studies suggest that syngeneic GVHD has significant antitumor activity.
11,12
Moreover, the antitumor effect of this autoaggression syndrome can be enhanced by the administration of cytokines that upregulate the expression of the MHC Class II target antigen on the tumor cell.
6,7
Clinical trials are currently underway to evaluate the antitumor immunotherapeutic potential of autologous GVHD in man.
8-12
Thee is a need in the art for additional tools and methods to modulate the anti-tumor immune response found in syngeneic GVHD.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide polypeptides for stimulating an immune response.
It is another object of the present invention to provide polypeptides for suppressing an immune response.
It is an object of the present invention to provide methods of modulating an immune response.
Another object of the invention is to provide a vaccine for inducing an immune response to an antigen.
Another object of the invention is to provide method for screening compounds to identify those which will modulate a cellular immune response.
Another object of the invention is to provide an antibody which is useful for suppressing an immune response.
Another object of the invention is to provide a method to monitor cyclosporin therapy.
It is still another object of the invention to provide polynucleotide molecules which encode CLIP polypeptides.
These and other objects of the invention are achieved by one or more of the embodiments described below. In one embodiment a polypeptide is provided. The polypeptide comprises a first and second segment. The first segment consists of amino acid residues of the invariant chain of MHC class II selected from SEQ ID NO: 1 and comprises the sequence VSP. The second segment comprises an antigen. Alternatively the first segment consists of amino acid residues of the invariant chain of MHC class II selected from SEQ ID NO: 5 and comprises the sequence VSK.
According to another embodiment of the invention a polypeptide is provided which consists of a segment of the invariant chain of MHC class II. The segment contains 3 to 28 contiguous amino acid residues selected from SEQ ID NO: 1 and comprises the sequence VSP. Alternatively, the segment contains 3 to 28 contiguous amino acid selected from SEQ ID NO: 5 and comprises the sequence VSK.
In another embodiment of the invention a method is provided for modulating an immune response. The method comprises the step of contacting T cells with a polypeptide. The polypeptide comprises a segment of the invariant chain of MHC class II. The segment consists of 3 to 29 contiguous amino acid residues selected from SEQ ID NO: 1 and comprises the sequence VSP. Alternatively, the segment consists of 3 to 29 contiguous amino acid residues selected from SEQ ID NO: 5 and comprises the sequence VSK.
According to another aspect of the invention, a vaccine is provided for inducing an immune response to an antigen. The vaccine comprises a polypeptide which comprises a first and second segment. The first segment consists of amino acid residues of the invariant chain of MHC class II selected from SEQ ID NO: 1 and comprises the sequence VSP. The second segment comprises an antigen. Alternatively, the first segment consists of amino acid residues of the invariant chain of MHC class II selected from SEQ ID NO: 5 and comprises the sequence VSK. The polypeptide is suspended in a pharmaceutically acceptable carrier.
In still another aspect of the invention, a method is provided for screening compounds to identify those which will modulate a cellular immune response. The method comprises the step of contacting a CLIP polypeptide as shown in SEQ ID NO: 1, or a portion of a CLIP polypeptide comprising VSP, with an &agr;/&bgr; T Cell Receptor and a test compound. The amount of binding of the CLIP polypeptide (or portion) bound to the &agr;/&bgr; T Cell Receptor is determined. A test compound which reduces the amount of binding is identified as a candidate immunosuppressant. A test compound which increases the amount of binding is identified as a candidate immunostimulant.
Another embodiment of the invention is an antibody. The antibody specifically binds to a CLIP polypeptide as shown in SEQ ID NO: 1 or SEQ ID NO: 5, and inhibits binding of the CLIP polypeptide to MHC class II or T Cell Receptor.
In still another aspect of the invention a polypeptide is provided. The polypeptide comprises a segment of the invariant chain of MHC class II selected from SEQ ID NO: 1. However, the segment does not contain the sequence VSP. Alternatively, the segment of the invariant chain of MHC class II is selected from SEQ ID NO: 5, and the segment does not comprises the sequence VSK.
In still another embodiment of the invention, a method is provided for modulating an immune response. T cells are contacted with a polypeptide comprising a segment of the invariant chain of MHC class II. The segment consists of amino acid residues selected from SEQ ID NO: 1. However, the segment does not contain the sequence VSP. Alternatively, the segment consists of amino acid residues selected from SEQ ID NO: 5 and wherein the segment does not contain the sequence VSK.
In even another embodiment of the invention a polynucleotide is provided. The polynucleotide encodes any of the CLIP derived polypeptides described herein. The CLIP derived polypeptides may be the full-length CLIP polypeptide of 29 amino acids, a truncated version of CLIP having an N-terminal, a C-terminal or an internal deletion.
A method of monitoring cyclosporin therapy is yet another aspect of the invention. The method involves testing a sample of T cells for the ability to bind to CLIP polypeptide as shown in SEQ ID NO: 5. The T cells are isolated from a patient receiving cyclosporin therapy. The amount of T cells which bind to CLIP polypeptide indicate the patient's responsiveness to cyclosporin.
These and other embodiments of the invention, which are described more fully below, provide the art with tools and methods for treating a variety of immune and non-immune based diseases. In addition, tools are provided for discovering small molecules with immune modulatory activity.
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Accession
Banner & Witcoff , Ltd.
DeCloux Amy
Saunders David
The Johns Hopkins University
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