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Compositions and methods for WT1 specific immunotherapy

A compositional and specific technology, applied in the field of RM, ALLPAVSSL, immunotherapy for malignant diseases such as leukemia and cancer, MTSQL, can solve the problems that have not shown therapeutic benefit

Inactive Publication Date: 2005-09-21
CORIXA CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, relatively few TAAs are known to date, and the generation of an immune response against this antigen has, with rare exceptions, shown no therapeutic benefit

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

[0246] Identification of immune responses against WT1 in patients with hematological malignancies

[0247] This example illustrates the identification of preexisting immune responses in patients with hematological malignancies.

[0248] To assess the presence of pre-existing WT1-specific antibody responses in patients, samples from acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and severe aplastic leukemia were analyzed by Western blot analysis. Sera from anemic patients. Sera were tested for their ability to immunoprecipitate WT1 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-WTA1 antibody WT180 (Santa Cruz Biotechnology, Inc., Santa Cruz, CA). This western blot analysis identifies potential WT1-specific antibodies in patients with hematologic malignancies. A repre...

Embodiment 2

[0259] Induction of antibodies against WT1 in mice immunized with a WT1-expressing cell line

[0260] This example illustrates the use of cells expressing WT1 to induce a WT1-specific antibody response in vivo.

[0261] Detection of preexisting antibodies against WT1 in leukemia patients strongly suggests the possibility of immunity to WT1 protein to elicit 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 treated with 5 × 10 6 Tramp-C cells were subcutaneously immunized with 5×10 6 Cells were boosted twice at 3 week intervals. Three weeks after the last immunization, serum was obtained and spleen single cell suspension was prepared in RPMI 1640 medium (GIBCO) with 25 μM β-2-mercaptoethanol, 200 units of penicillin per ml, 10 mM L-glutamine and 10% fetal bovine serum.

[0262] Following TRAMP-C immunization, WT1-specific antibody r...

Embodiment 3

[0264] T in mice immunized with WT1 peptide H and induction of antibody responses

[0265] This example illustrates the ability of immunization with WT1 peptide to elicit a WT1-specific immune response.

[0266] Peptides suitable for eliciting Ab and proliferative T cell responses were identified according to the Tsites procedure (Rothbard and Taylor, EMBO J. 7:93-100, 1988; Deavin et al., Mol. Immunol. 33:145-155, 1996), which The program looks for peptide motifs with the potential to elicit a Th response. The peptides shown in Table I were synthesized and sequenced.

[0267] Table I

[0268] peptide

sequence

note

Mouse: p6-22

RDL NALLPAVSSLGGGG

(SEQ ID NO: 13)

relative to the human WT1 sequence

has 1 mismatch

Human: p6-22

RDL NALLPAVPSLGGGG

(SEQ ID NO: 1)

Human / mouse: p117-139

PSQASSGQARMFPNAPYLPSC

LE (SEQ ID NO: 2 and 3)

Mouse: p244-262

GATLKGMAAGSSSSVKWTE

(SEQ ID NO: 14)

...

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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] Statement Regarding Federally Sponsored Research or Development [0002] This invention was made in part with government support under NIH SBIR Phase I Grant No. IR43 CA81752-01 Al. The government has certain rights in this invention. Background of the invention [0003] technical field of invention [0004] The present invention relates generally to immunotherapy of malignant diseases such as leukemia and cancer. The present invention more particularly relates to a composition for generating and enhancing an immune response to WT1, and to the use of this composition for preventing and / or treating malignant diseases. [0005] Description of related technologies [0006] Cancer and leukemia are important health problems in the United States and worldwide. Despite advances in the detection and treatment of these diseases, there are currently no vaccines or other generally successful methods for preventing or treating cancer and leukemia. Management of these diseas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/00C07K11/00C07K7/00A61K48/00C12N15/09A61K35/76A61K38/00A61K39/00A61P35/00A61P35/02C07K14/47C07K14/82C07K19/00C12N1/15C12N1/19C12N1/21C12N5/08C12N5/10
CPCC07K2319/00C07K14/4748A61K48/00A61K38/00A61K2039/515A61K39/00A61P35/00A61P35/02A61P37/00C07K14/47C07K14/435
Inventor A·盖格尔P·D·麦克尼尔N·加亚D·卡特尔
Owner CORIXA CORP
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