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Modified MELK peptides and vaccines containing the same

An HLA-A24, amino acid technology, applied in the direction of peptides, peptide/protein components, medical preparations containing active ingredients, etc.

Active Publication Date: 2012-12-12
ONCOTHERAPY SCI INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, it has been significantly shown that inhibition of MELK expression with siRNA results in the growth of human breast cancer cells

Method used

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  • Modified MELK peptides and vaccines containing the same
  • Modified MELK peptides and vaccines containing the same
  • Modified MELK peptides and vaccines containing the same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0412] Materials and methods

[0413] cell line

[0414] Human leukocyte antigen (HLA)-A*2402 positive B-lymphoblastoid cell line TISI was purchased from IHWG Cell and Gene Bank (Seattle WA). OS7, MDA-MB-435S and T47D were purchased from ATCC. KLM-1 and KP-1N were purchased from RIKEN Cell Bank and JCRB Cell Bank, respectively.

[0415] Candidate selection for peptides derived from MELK

[0416] 9-mer and 10-mer peptides derived from MELK that bind HLA-A*2402 molecules were predicted using the binding prediction software "BIMAS" (www-bimas.cit.nih.gov / molbio / hla bind), developed by Parker described by et al. (J Immunol 1994, 152(1): 163-75) and Kuzushima et al. (Blood 2001, 98(6): 1872-81). An HIV peptide restricted by HLA-A*2402 (RYLRQQLLGI (SEQ ID NO: 48)) was used as a control. These peptides were synthesized by Biosynthesis (Lewisville, TX) according to standard solid phase synthesis and purified by reverse phase high performance liquid chromatography (HPLC). T...

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Abstract

Isolated peptides composed of the amino acid sequence of the modified MELK epitope peptide or immunologically active fragments thereof that bind to HLA antigens and have higher cytotoxic T lymphocyte (CTL) inducibility than that of the wild type MELK epitope peptide and thus are suitable for use in the context of cancer immunotherapy or endometriosis immunotherapy, more particularly cancer or endometriosis vaccines are described herein. The present invention further provides peptides that include one, two, or several amino acid insertions, substitutions or additions to the aforementioned peptides or fragments, but yet retain the requisite cytotoxic T cell inducibility. Further provided are nucleic acids encoding any of these aforementioned peptides as well as pharmaceutical substances and compositions including any of the aforementioned peptides or nucleic acids. The peptides, nucleic acids, pharmaceutical substances and compositions of this invention find particular utility in the treatment of cancers, tumors, and endometriosis.

Description

technical field [0001] The present invention relates to the field of biological sciences, more specifically to the field of cancer treatment. In particular, the present invention relates to novel peptides that are extremely useful as cancer vaccines, and drugs for the treatment and prevention of tumors (or diseases involving MELK expression). [0002] priority [0003] This application claims the benefit of US Provisional Application 61 / 297,996, filed January 25, 2010, the entire contents of which are hereby incorporated by reference. Background technique [0004] It has been demonstrated that CD8-positive cytotoxic T cells (CTLs) can recognize epitope peptides derived from tumor-associated antigens (TAAs) appearing on major histocompatibility complex (MHC) class I molecules, and then kill tumor cells. Since the discovery of the first example of a TAA, the melanoma antigen (MAGE) family, many other TAAs have been discovered mainly by immunological means (NPL1,2). Some of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K38/00A61P35/00
CPCA61K39/0011C12N9/1205C12N9/00A61K39/39C12Y207/11025A61P15/00A61P15/08A61P35/00A61K39/001162A61K38/08C07K7/06
Inventor 中村佑辅角田卓也大泽龙司吉村祥子渡边朝久
Owner ONCOTHERAPY SCI INC
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