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Compositions and methods for wt1 specific immunotherapy

A composition, the same technology, used in the prevention and/or treatment of malignant diseases, the field of compositions for generating or promoting an immune response to WT1, can solve the problems of immune response having a therapeutic effect, TAA has not been confirmed, etc.

Inactive Publication Date: 2004-06-16
CORIXA CORP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, to date little is known about TAAs and immune responses against these antigens have not been shown to be therapeutically effective, except in rare

Method used

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  • Compositions and methods for wt1 specific immunotherapy
  • Compositions and methods for wt1 specific immunotherapy
  • Compositions and methods for wt1 specific immunotherapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0157] Identification of immune responses to WT1 in blood cancer patients

[0158] This example illustrates the identification of immune responses present in cancer patients.

[0159] To evaluate the presence of pre-existing WT1-specific antibodies in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and severe regenerative Sera from patients with obstructive anemia. Test sera were tested for the ability to immunoprecipitate from the human leukemia cell line K562 (American Type Culture Collection, Manassas, VA). In each case, immunoprecipitates were separated by gel electrophoresis, transferred to membranes and probed with anti-WT1 antibody WT180 (Santa Cruz Biotechnology, Inc., Santa Cruz, CA). This western blot analysis identified potential WT1-specific antibodies in blood cancer patients. A representative Western blot showing the results of patients with AML is shown in Figure 2. The 52 kD protein in immunopre...

Embodiment 2

[0170] Induction of antibodies against WT1 in mice immunized with a WT1-expressing cell line

[0171] This example illustrates the use of cells expressing WT1 to induce WT1-specific antibody responses in vivo.

[0172] The detection of antibodies against WT1 in leukemia patients strongly suggests that immunization with WT1 protein may induce immunity to WT1. To test whether immunity to WT1 could be generated by immunization, mice were injected with TRAMP-C, a WT1-positive tumor cell line derived from B6. Briefly, male B6 mice were immunized subcutaneously with 5 × 10 6 TRAMP-C cells were boosted twice at 3-week intervals with 5×10 6 cells. Serum was collected 3 weeks after the final immunization and spleens were prepared in RPMI 1640 medium (GIBCO) containing 25 μM β-2-mercaptoethanol, 200 units penicillin / ml, 10 mM L-glutamine and 10% fetal bovine serum. single cell mixture.

[0173] Following immunization with TRAMP-C, WT1-specific antibody responses could be detected i...

Embodiment 3

[0175] Induction of TH and antibody responses in mice immunized with WT1 peptide

[0176] This example illustrates the ability of immunization with WT1 peptide to elicit an immune response specific for WT1.

[0177] According to the Tsites procedure (Rothbard and Taylor, EMBO J. 7:93-100, 1988; Deavin et al., Mol. Immunol. 33:145-155, 1996 ) identifies peptides suitable for eliciting Ab and proliferative T cell responses, a program that searches for peptide motifs with the ability to elicit Th responses. The peptides shown in Table I were synthesized and sequenced.

[0178] Table I

[0179] peptide

sequence

Notes

Mouse: p6-22

RDL NALLPAVSSLGGGG

(SEQ ID NO: 13)

Compared to human WT1 sequence

1 mismatch

People: p6-22

RDL NALLPAVPSLGGGG

(SEQ ID NO: 1)

Human / Mouse:

p117-139

PSQASSGQARMFPNAPYLPSCLE

(SEQ ID NOs: 2 and 3)

Mouse: p244-

262

GATLKGMAAGSSSSVKWTE

(SEQ ID NO: 14)

Compa...

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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.

Description

[0001] Information about federally funded research or development [0002] This invention was made in part with government support under NIH SBIR Phase I grant number IR43CA81752-01A1. The government may have certain rights in this invention. technical field [0003] The present invention generally relates to immunotherapy of malignant diseases such as leukemia and cancer. More specifically, the present invention relates to compositions for generating or promoting an immune response to WT1 and to the use of such compositions in the prevention and / or treatment of malignant diseases. Background technique [0004] Cancer and leukemia are major health problems in the United States and around the world. Despite advances in detection and treatment of these diseases, there are currently no vaccines or other generally successful methods for preventing or treating cancer and leukemia. Control of this disease currently relies on a combination of early diagnosis and aggressive thera...

Claims

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Application Information

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IPC IPC(8): G01N33/574A61K31/7088A61K35/14A61K38/00A61K39/00A61K39/39A61K39/395A61K45/00A61K48/00A61P35/00A61P35/02A61P37/04C07K14/47C07K14/82C07K16/32C07K19/00C12N1/15C12N1/19C12N1/21C12N5/10C12N15/09C12Q1/68
CPCC07K2319/00C07K14/4748A61K48/00A61K38/00A61K2039/515A61K39/00A61P35/00A61P35/02A61P37/04A61P43/00A61K39/464453A61K39/4611C07H21/04
Inventor 亚历山大·盖杰P·D·迈克内尔M·史密斯戈尔G·莫尔顿T·S·韦德维克P·R·斯莱斯S·莫斯曼L·埃文斯A·G·斯皮斯J·伯伊斯顿
Owner CORIXA CORP
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