Compositions and methods for wt1 specific immunotherapy
OwnerAlexander Gaiger, Martin A. Cheeverinventors
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Abstract
Compositions and methods for the therapy of malignant diseases, such as leukemia and cancer, are disclosed. The compositions comprise one or more of a WT1 polynucleotide, a WT1 polypeptide, an antigen-presenting cell presenting a WT1 polypeptide, an antibody that specifically binds to a WT1 polypeptide; or a T cell that specifically reacts with a WT1 polypeptide. Such compositions may be used, for example, for the prevention and treatment of metastatic diseases.
Claims16
A polypeptide comprising an immunogenic portion of a native WT1, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with WT1-specific antisera and/or T-cell lines or clones is not substantially diminished, wherein the polypeptide comprises no more than 16 consecutive amino acid residues present within a native WT1 polypeptide.
A polypeptide comprising an immunogenic portion of amino acid residues 1-174 of a native WT1 polypeptide, or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with WT1 specific T-cell lines or clones is not substantially diminished, wherein the polypeptide comprises no more than 16 consecutive amino acid residues present within amino acids 175-449 of the native WT1 polypeptide.
A pharmaceutical composition, comprising:
- (a) a first component selected from:
- a. a polynucleotide encoding a WT1 polypeptide, wherein the polypeptide comprises an immunogenic portion of a native WT1 or a variant thereof that differs in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with antigen-specific antibodies and/or T cell lines or clones is not substantially diminished;
- b. an antibody or antigen-binding fragment thereof that specifically binds to a WT1 polypeptide;
- c. a T cell that specifically reacts with a WT1 polypeptide;
- d. a WT1 polypeptide that comprises an immunogenic portion of a native WT1 or variant thereof that differs in one or more substitutions, deletions, additions, and/or insertions such that the ability of the variant to react with antigen-specific antibodies and/or T cell lines or clones is not substantially diminished;
- and
- (b) a pharmaceutically acceptable carrier or excipient.
A method for stimulating and/or expanding T cells, comprising contacting T cells with a WT1 polypeptide, a polynucleotide encoding a WT1 polypeptide and/or an antigen presenting cell that expresses a WT1 polypeptide under conditions and for a time sufficient to permit the stimulation and/or expansion of the T cells.
A method for stimulating and or expanding T cells in a mammal, comprising administering to a mammal a pharmaceutical composition comprising:
- (a) one or more of:
- (i) a WT1 polypeptide;
- (ii) a polynucleotide encoding a WT1 polypeptide;
- or
- (iii) an antigen-presenting cell that expresses a WT1 polypeptide;
- and
- (b) a physiologically acceptable carrier or excipient;
- and thereby stimulating and/or expanding T cells in a mammal.
A method for inhibiting the development of a malignant disease associated with WT1 expression in a patient, comprising administering to a patient cells expressing T cell receptors for T cells specific for WT1.
Dependencies are inferred from the claim text.