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Cancer vaccine composition

A cancer vaccine and composition technology, which can be used in vaccines, drug combinations, DNA/RNA vaccination, etc., and can solve problems such as unreported WT1 modified peptides

Active Publication Date: 2010-11-17
INT INST OF CANCER IMMUNOLOGY INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0022] However, it has never been reported whether these WT1 modified peptides can be used to bind to other types of HLAs besides HLA-A*2402, HLA-A*0201, HLA-A*3303 and HLA-A*1101 and induce CTL responses cancer antigen

Method used

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  • Cancer vaccine composition
  • Cancer vaccine composition
  • Cancer vaccine composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0301] Example 1 (Prediction of HLA Molecules Capable of Binding to WT1 Peptide)

[0302] able to work with WT1 187 The HLA molecules bound by the peptide (SEQ ID NO: 2) were predicted using the NetMHC2.0 server prediction program.

[0303] As a result, HLA-A*0201-restricted WT1 capable of inducing WT1-specific CTLs 187 Peptides, in terms of binding affinity to HLA-A*0206 molecules, were predicted in the NetMHC2.0 server ( http: / / www.cbs.dtu.dk / services / NetMHC-2.0 / ) is sorted higher.

Embodiment 2

[0304] Example 2 (preparation of WT1 from PBMCs of HLA-A*0206 positive healthy blood donors 187 Peptide-specific CTLs, and cytotoxicity assays of CTLs)

[0305] (1) Separation of PBMCs from HLA-A*0206 positive healthy blood donors, and preparation of DCs

[0306] First, PBMCs were isolated from the peripheral blood of each HLA-A*0206 healthy blood donor (three individuals) by Ficoll-Hypaque density gradient centrifugation. Then, CD14-positive cells were selected from the PBMCs using anti-human CD14 magnetic beads-DM (manufactured by Becton, Dickinson and company (BD)). In this case, it is considered that a large number of CD14-positive cells are present in the monocyte population. The selected CD14-positive cells were cultured in X-VIVO15 medium (manufactured by BioWhittaker, Walkersville, MD), supplemented with 1v / v% human AB serum, 800IU / mL GM-CSF (manufactured by Pepro Tech INC, Rocky Hill, NJ) and 1000 IU / mL IL-4 (manufactured by Pepro Tech INC), to prepare DCs.

[030...

Embodiment 3

[0332] Example 3 (verification limit WT1 187 HLA type of peptide-specific CTLs)

[0333] WT1 obtained in Example 2 was examined 187 Is the cytotoxic activity of peptide-specific CTLs restricted by class I HLA. performed in the presence or absence of mAbs against HLA class I or HLA class II 51 Cr release cytotoxicity test. Autologous B-LCLs were used as target cells. In this experiment, the E / T ratio was 5:1.

[0334] The results are shown in Figure 4 middle. Figure 4 a shows the use of B-LCLs (not expressing WT1 187 , HLA-A*0206 positive) as target cells, the results of experiments performed in the absence of mAbs against class I HLA (anti-HLA class I mAbs) and mAbs against HLA class II (anti-HLA class II mAbs) . Figure 4 b shows the use of WT1 187 Peptide-pulsed B-LCLs (expressing WT1 187 , HLA-A*0206 positive) as target cells, the results of experiments performed in the absence of anti-HLA class I mAbs and in the presence of anti-HLA class II mAbs. Figure 4 c...

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Abstract

Disclosed is a cancer vaccine composition for a human leukocyte antigen (HLA)-A*0206-positive subject, which is characterized by comprising a protein which is a gene product of a tumor suppressor gene WT1 or a partial peptide of the protein.

Description

technical field [0001] The present invention relates to a cancer vaccine composition for human leukocyte antigen (HLA)-A*0206-positive persons, comprising a protein product of the tumor suppressor gene Wilms' tumor 1 (WT1) (hereinafter sometimes abbreviated as WT1 protein) or a partial peptide thereof (hereinafter sometimes abbreviated as WT1 peptide). The present invention also relates to a cancer vaccine composition for HLA-A*0206-positive persons, comprising DNA or RNA encoding the above-mentioned WT1 protein or WT1 peptide, and a method for inducing WT1-specific CTLs, for inducing presentation A method for dendritic cells of cancer antigens, a method for diagnosing cancer in HLA-A*0206-positive persons, and a method for treating or preventing cancer in HLA-A*0206-positive persons. [0002] The present invention also relates to a cancer vaccine composition for HLA-A*0201 positive persons comprising a modified peptide of the WT1 peptide. Background technique [0003] The...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61K39/39A61P35/00A61P35/02C07K7/06G01N33/574
CPCC07K14/4748C07K7/06A61K39/0011G01N33/56972G01N33/574A61K2039/53A61K39/4615A61K39/464453C12N5/0638A61K2239/48A61K39/4611C12N5/0639A61K39/4622A61P35/00A61P35/02A61P37/04A61K38/08G01N33/57496C12N2501/40A61K2039/54A61K2039/545A61K39/001153A61K35/15A61K35/17A61K2039/5154A61K2039/5158
Inventor 杉山治夫
Owner INT INST OF CANCER IMMUNOLOGY INC
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