Partial peptide of survivin presented on mhc class ii molecule and use therof

a technology of survivin and peptide, which is applied in the field of antigenic polypeptide, can solve the problem that cancer immunotherapy cannot be said to be promising, and achieve the effect of promoting the production of cytokines, stable and inexpensiv

Inactive Publication Date: 2011-02-03
TELLA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0029]The peptide of the present invention induces Th cells specific to Survivin (hereinafter referred to as Sur / Th cells) by incubating the peptide with antigen-presenting cells and CD4-positive T cells and has an activity to produce cytokines in the Sur / Th cells. Since the Sur / Th cells specifically attacks the malignant neoplasms expressing Survivin, the Peptide of the present invention can be used as an ingredient of a therapeutic agent for malignant neoplasms.
[0030]Since the polypeptide of the present invention, having a small number of constituent amino acid residues, can be produced in large quantities not only by gene recombination techniques but also by organic synthetic methods, the polypeptide can be supplied in clinical studies and applications stably and inexpensively.
[0031]A therapeutic agent for malignant neoplasms comprising the polypeptide of the present invention, by combining tumor antigens with Th cells specific to the tumor antigens, can more strongly promote the production of cytokines in the Th cells. The cytokines produced induce in vivo antitumor immune response specific to the malignant neoplasms expressing the tumor antigens to cause regression of the tumor.

Problems solved by technology

However, since tyrosinase is expressed only in limited types of tumors, it can hardly be said to be a promising cancer antigen in cancer immunotherapy.

Method used

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  • Partial peptide of survivin presented on mhc class ii molecule and use therof
  • Partial peptide of survivin presented on mhc class ii molecule and use therof
  • Partial peptide of survivin presented on mhc class ii molecule and use therof

Examples

Experimental program
Comparison scheme
Effect test

example 1

Identification of SU18

1) Synthesis of Peptide

[0074]From the N terminus to C terminus of Survivin, total of 25 types (referred to as SU1 to SU27) of 19 to 20-amino acid residue peptide (Table 1) having an overlapping sequence of 7 to 8 amino acids at the C terminus and / or N terminus were designed, for example, a peptide composed of 1st to 20th amino acid sequence of Survivin-2B (SEQ ID NO:56), a peptide composed of 8th to 27th amino acid sequence thereof, and a peptide composed of 14th to 34th amino acid sequence thereof, each of which was chemically synthesized.

TABLE 1MIX1SU1MGAPTLPPAWQPFLKDHRISSequence No. 1SU2PAWQPFLKDHRISTFKNWPFSequence No. 2SU3LKDHRISTFKNWPFLEGCASequence No. 3SU4FKNWPFLEGCACTPERMAEASequence No. 4SU5EGCACTPERMAEAGFIHCPSequence No. 5MIX2SU6PERMAEAGFIHCPTENEPDLSequence No. 6SU7GFIHCPTENEPDLAQCFSequence No. 7SU8PTENEPDLAQCFFCFKELESequence No. 8SU9DLAQCFFCFKELEGWEPDSequence No. 9SU10FFCFKELEGWEPDDDPIGSequence No. 10MIX3SU11ELEGWEPDDDPIGPGTVAYASequence No. 11SU12DDDPI...

example 2

Examination of HLA-DRB1*0101-Restricted SU18 Recognition Site

1) Confirmation of HLA-Restrictivity

[0084]HLA-restrictivity for SU18 was confirmed by using inhibitory antibodies and the Th cell group obtained in Example 1-4) comprising Sur / Th cells which react specifically with SU18.

[0085]In a 96-well U-bottom plate (BD Biosciences) with 200 μL of 5% human serum in AIM-V, each of anti-HLA-DP antibodies (Serotech), anti-HLA-DQ antibodies (Serotech) and anti-HLA-DR antibodies (BD Biosciences) was added, to a final concentration of 5 μg / mL, to the PBMCs (1×105 cells / well) and the above-described Th cell group (5'104 cell / well) comprising Sur / Th cells which react specifically with SU18. The resultants were co-cultured in the presence of SU18 peptides in a CO2 incubator at 37° C. for 24 hours. After the culturing, the IFN-γ contained in the culture supernatant was measured by using an ELISA kit (BD Biosciences). The results are shown in FIG. 3.

[0086]As shown in FIG. 3, the inhibition of IFN...

example 3

Examination of HLA-DRB1*1201 / HLA-DRB1*1502-Restricted SU18 Recognition Site

1) Establishment of Th Cell Group Comprising Sur / Th Cells

[0093]By the 28-day co-culture according to the method described in Example 1-2) and 3), a Th cell group comprising Sur / Th cells was prepared from peripheral blood of a healthy individual whose HLA genotype is HLA-DRB1*1201 / HLA-DRB1*1502. Further, to establish a single cell group, a 96-well U-bottom plate was provided with the culture containing 200 μL of the complex medium of human serum and fetal calf serum (2.5% human serum, 2.5% fetal calf serum in AIM-V), PBMCs-Ad (5×104 cells / well), recombinant IL-2 (final concentration of 20U / mL), recombinant IL-7 (final concentration of 10 ng / mL), and phytohemagglutinin (PHA, SEIKAGAKU Co., final concentration of 5 μg / mL). The Th cell group (1 cell / well) was added thereto and the resultant was co-cultured in a CO2 incubator at 37° C.

[0094]After 14 days from the start of the co-culture, the wells which showed bla...

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Abstract

The object aims to provide: a novel tumor antigen; a novel therapeutic agent useful in a method for treating a malignant neoplasm by utilizing the tumor antigen; and a tumor antigen which can be used as the therapeutic agent. Thus, disclosed are: a novel tumor antigen which has an epitope capable of inducing a Th1 cell which is a CD4-positive T cell specific to Survivin; and use of the tumor antigen. Specifically disclosed is a polypeptide which comprises an amino acid sequence depicted in SEQ ID NO:17 or the like and has an activity to cause the production of a cytokine by a Th cell that is a cell specific to Survivin. The peptide can induce a Th cell that is specific to Survivin and can cause the production of a cytokine by the Sur / Th cell when the peptide is incubated together with an antigen-presenting cell and a CD4-positive T cell.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This is a U.S. national application under 35 U.S.C. §371 of International Application No. PCT / JP2009 / 056649, filed Mar. 31, 2009, which claims priority to Japanese Application No. 2008-093292, filed Mar. 31, 2008, the contents of each of which are incorporated by reference in their entirety.FIELD OF THE INVENTION[0002]The present invention relates to an antigenic polypeptide that can be used in cancer immunotherapy and to a therapeutic agent for malignant neoplasms comprising the polypeptide.BACKGROUND OF THE INVENTION[0003]One of the therapeutic methods for cancers (malignant neoplasms), an intractable disease, includes so-called cancer immunotherapy which causes regression of cancer cells by utilizing an immune system of individual patients. The important point in this method is how to make the immune system recognize the cancer cells as foreign and induce immune cells that are aggressive to the cancer cells.[0004]Key immune cells invol...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00C07K7/08C07K14/00C12N15/12C12N15/63C07K16/18C12N5/0783A61K35/12A61P35/00
CPCA61K38/00A61K39/00C07K14/4747C12N2501/998A61K39/0011C12N5/0636C07K14/4748A61K39/00115A61P35/00A61P37/04C07K7/08C07K14/47
Inventor NISHIMURA, TAKASHI
Owner TELLA INC
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