Compositions and methods for WT1 specific immunotherapy
View Patent ↗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.
1. A method for enhancing or inducing an immune response in a human patient, comprising administering to a patient a composition comprising:
(a) a WT1 polypeptide consisting of an immunogenic portion of a native WT1, wherein the immunogenic portion consists of the consecutive amino acids of SEQ ID NO:144; and
(b) a physiologically acceptable carrier or excipient;
and thereby enhancing or inducing an immune response specific for WT1 or a cell expressing WT1 in the human patient.
2. A method for enhancing or inducing an immune response in a human patient, comprising administering to a patient a composition comprising:
(a) a WT1 polypeptide consisting of an immunogenic portion of a native WT1, wherein the immunogenic portion consists of the consecutive amino acids of SEQ ID NO:144; and
(b) a non-specific immune response enhancer;
and thereby enhancing or inducing an immune response specific for WT1 or a cell expressing WT1 in the human patient.
3. A method for stimulating and/or expanding T cells comprising contacting T cells with a WT1 polypeptide, wherein said WT1 polypeptide consists of an immunogenic portion of native WT1, wherein the immunogenic portion consists of the consecutive amino acids of SEQ ID NO:144, under conditions and for a time sufficient to permit the stimulation and/or expansion of T cells.
4. A method according to claim 3 , wherein the T cells are present within the bone marrow, peripheral blood or a fraction of bone marrow or peripheral blood.
5. A method according to claim 4 , wherein the bone marrow, peripheral blood or fraction is obtained from a patient afflicted with a malignant disease associated with WT1 expression.
6. A method according to claim 4 , wherein the bone marrow, peripheral blood or fraction is obtained from a mammal that is not afflicted with a malignant disease associated with WT1 expression.
7. A method according to claim 3 , wherein the T cells are cloned prior to expansion.
8. A method for stimulating and/or expanding T cells in a mammal, comprising administering to a mammal a composition comprising a WT1 polypeptide, wherein said WT1 polypeptide consists of an immunogenic portion of native WT1, wherein the immunogenic portion consists of the consecutive amino acids of SEQ ID NO:144 and a physiologically acceptable carrier or excipient; and thereby stimulating and/or expanding T cells in a mammal.
9. A method for stimulating and/or expanding T cells in a mammal, comprising administering to a mammal a composition comprising a WT1 polypeptide, wherein said WT1 polypeptide consists of an immunogenic portion of native WT1, wherein the immunogenic portion consists of the consecutive amino acids of SEQ ID NO:144 and a non-specific immune response enhancer; and thereby stimulating and/or expanding T cells in a mammal.
10. The method of claim 1 wherein said physiologically acceptable carrier comprises a biodegradable microsphere.
11. The method of claim 2 wherein said non-specific immune response enhancer is selected from the group consisting of alum-based adjuvants, oil based adjuvants, nonionic block copolymer-based adjuvants, dimethyl dioctadecyl ammoniumbromide based adjuvants, saponin based adjuvants, muramyl dipeptide based adjuvants, human complement based adjuvants, inactivated toxins, and attenuated infectious agents.
12. The method of claim 8 wherein said physiologically acceptable carrier comprises a biodegradable microsphere.
13. The method of claim 9 wherein said non-specific immune response enhancer is selected from the group consisting of alum-based adjuvants, oil based adjuvants, nonionic block copolymer-based adjuvants, dimethyl dioctadecyl ammoniumbromide based adjuvants, saponin based adjuvants, muramyl dipeptide based adjuvants, human complement based adjuvants, inactivated toxins, and attenuated infectious agents.
14. A method for enhancing or inducing an immune response in a human patient, comprising administering to a patient a composition comprising:
(a) a WT1 polypeptide consisting of an immunogenic portion of a native WT1, wherein the immunogenic portion consists of the consecutive amino acids of SEQ ID NO:144; and
(b) a physiologically acceptable carrier comprising a microsphere; and
(c) a non-specific immune response enhancer;
and thereby enhancing or inducing an immune response specific for WT1 or a cell expressing WT1 in the human patient.
15. A method for stimulating and/or expanding T cells in a mammal, comprising administering to a mammal a composition comprising a WT1 polypeptide consisting of:
(a) an immunogenic portion of native WT1 consisting of the consecutive amino acids of SEQ ID NO:144;
(b) a physiologically acceptable carrier comprising a microsphere; and
(c) a non-specific immune response enhancer;
and thereby stimulating and/or expanding T cells in a mammal.
16. An immunogenic composition comprising a polypeptide consisting of SEQ ID NO:144 in combination with a non-specific immune response enhancer.
17. The immunogenic composition according to claim 16 wherein the non-specific immune response enhancer is preferentially enhances a T cell response.
18. The immunogenic composition according to claim 17 wherein the non-specific immune response enhancer is selected from the group consisting of cytokines, dimethyl dioctadecyl ammoniumbromide (DDA) based adjuvants, saponin based adjuvants, and inactivated toxins.