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Immunogenic peptides derived from the midkine protein, as an anticancer vaccine

A midkine and protein technology, applied in animal/human proteins, cancer antigen components, vertebrate antigen components, etc., can solve the problem that the immunogenicity of midkine protein has not been studied.

Inactive Publication Date: 2011-07-13
法国原子能与替代能源委员会
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0022] On the other hand, the immunogenicity of the midkine protein has not been studied

Method used

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  • Immunogenic peptides derived from the midkine protein, as an anticancer vaccine
  • Immunogenic peptides derived from the midkine protein, as an anticancer vaccine
  • Immunogenic peptides derived from the midkine protein, as an anticancer vaccine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0159] Example 1 : CD8 specific for midkine protein peptide + Induction of T response

[0160] Materials and Methods

[0161] a) peptide

[0162] Seven peptides represent potential CD8 restricted by HLA-A2 molecules + T epitopes, which are the most widely represented class I HLA alleles in the Caucasian population, were identified by using the BIMAS program ( http: / / www- bimas.cit.nih.gov ) is selected. Sequences of selected peptides are shown in Table IV and the accompanying Sequence Listing.

[0163] Table IV : list of selected peptides

[0164] peptide

sequence

SEQ ID NO:

MDK13-21

ALLALTSAV

4

MDK12-21

LALLALTSAV

3

MDK14-22

LLALTSAVA

6

MDK13-22

ALLALTSAVA

5

MDK114-122

AQCQETIRV

8

MDK113-122

NAQCQETIRV

7

MDK63-72

AQTQRIRCRV

17

[0165] These peptides were synthesized in solid phase parallel synthesis according to the Fmoc strat...

Embodiment 2

[0186] Example 2 : Detection of CD8 specific for midkine peptides by labeling with specific tetramers + T lymphocytes

[0187] Each lymphoid cell line (500000 cells) obtained in Example 1 was labeled with tetramer at 50 μg / ml in 200 μl PBS / 2% FCS in the dark at 4°C. These tetramers are biotinylated HLA-A2 molecules loaded with peptides 13-21 or 114-122 and complexed with phycoerythrin-tagged streptavidin, and according to Novak et al. (J.Clin.Investig ., 1999, 104, R63-R67) or the technique described in Kuroda et al. (J. Virol., 2000, 74, 18, 8751-8756). Cells were then washed twice in PBS before labeling with FITC anti-CD8 antibody (BD Biosciences) for 30 minutes at 4°C. After washing in PBS, cells were fixed with 50 [mu]l of PBS containing 1% paraformaldehyde (PAF). These markers were analyzed on a FACSCalibur flow cytometer (BD Biosciences). The results are shown in Figure 7 middle.

Embodiment 3

[0188] Example 3 : Induction of CD4 specific for peptides of the midkine protein + T-reaction

[0189] 1) Materials and methods

[0190] a) peptide

[0191] Coverage of human midkine (SwissProt P21741, SEQ ID NO: 2 and figure 1 ) peptides of 15 amino acids (15-mers) of the full sequence, selected based on the presence of aromatic or hydrophobic residues at positions 3 or 4, for use in the P1 pocket of HLA-DR and HLA-DP4 molecules mid anchor.

[0192] Selected peptide sequences are shown in Table V and the accompanying Sequence Listing.

[0193] Peptides were synthesized in solid-phase parallel synthesis according to the Fmoc strategy, purified by HPLC, and verified by mass spectrometry (ES-MS).

[0194] Table V : Selected peptides (SEQ ID NO: 9, 10, 13-15 and 18-30)

[0195]

[0196]

[0197] *Refers to the sequence of the 143 amino acid human midkine precursor (SwissProt P21741, figure 1 and SEQ ID NO: 2) to number the positions.

[0198] b) HLA II / pepti...

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Abstract

A peptide is derived from the Midkine protein, comprising at least one CD4<+>T or CD8<+>T epitope restricted by the HLA molecules predominant in the Caucasian population, or a polynucleotide encoding said peptide, as an anticancer vaccine or as a reagent for immunomonitoring of the cellular response against Midkine over the course of a cancer or of an anticancer treatment.

Description

technical field [0001] The present invention relates to the use of a peptide derived from the midkine protein, which induces the CD4 + T and / or CD8 + T lymphocytes, which recognize the midkine protein in a majority of individuals in the Caucasian population. [0002] The invention also relates to the presence of CD4, which is specific for the midkine protein, in a majority of individuals in the Caucasian population in many cancer types. + T and / or CD8 + The use of the peptide recognized by T lymphocytes as a reagent is used for immune monitoring of cancer or cell response to midkine during anticancer treatment. Background technique [0003] Tumor cells can express many proteins that healthy cells do not express, or express very little, or that are found in only a few cell types. These proteins that are preferentially expressed in tumor cells may constitute tumor antigens, ie proteins that are present in tumors and which induce an immune response capable of recognizing an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00C07K14/475A61P35/00
CPCA61K39/0011G01N33/56966G01N33/574G01N2333/475A61P1/04A61P1/16A61P1/18A61P11/00A61P13/08A61P13/10A61P15/00A61P19/00A61P25/00A61P35/00A61P35/02A61P37/04A61P5/00A61K39/4622A61K39/4611A61K39/4615A61K39/464499
Inventor 热罗姆·盖尔泽厚贝尔纳·马耶埃马纽埃尔·法夫里
Owner 法国原子能与替代能源委员会
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