PEPTIDE AND USE THEREOF
|Posted date||Oct 30, 2020|
|International application number||2020JP007917|
|International publication number||WO2020195504|
|Date of international filing||Feb 27, 2020|
|Date of international publication||Oct 1, 2020|
|Title||PEPTIDE AND USE THEREOF|
|Abstract||A peptide that has an amino acid sequence represented by general formula (I) and collects in cancer-related fibroblasts. (In general formula (I), X11 represents a peptide residue having the following amino acid sequence (a) or (b). (a) An amino acid sequence represented by any of SEQ ID NOS: 1 to 4, and (b) an amino acid sequence derived from an amino acid sequence represented by any of SEQ ID NOS: 1 to 4 by deletion, substitution or addition of one or two amino acids. Y11 represents a peptide linker consisting of 1-10, inclusive, amino acid residues, said amino acid residues being independently a glycine residue, a proline residue, a serine residue, a cysteine residue or a lysine residue. X12 represents a peptide residue having the aforesaid amino acid sequence (a) or (b), or a retroinverso peptide residue thereof. n11 is an integer of 0-9 inclusive.) [Formula 1]|
|Outline of related art and contending technology||
In Japan where the advanced age society has come, malignant neoplasm occupies the first place of the major cause of death, and 1 adults suffer from 2 adults. Among these malignancies, "skill cancer (hard cancer)" is expected to be solved as refractory cancer, which is resistant to current anticancer agent treatments. Subtypes of pancreatic cancer, gastric cancer, colorectal cancer, breast cancer and the like have been recognized as a representative of cancer of skill type showing the poor prognosis from pathological images of tumor tissues.
Skills cancer are well recognized by cancer clinicians as refractory type cancer which is still difficult to treat and has the lowest viability. In Japan, about 1 000 8000 persons are diagnosed as pancreatic cancer and about 4 000 5000 persons are diagnosed as stomach cancer (as skill type). According to the National Institute of Pancreatic Cancer Research,), there is a severe reality that all cases of Pancreatic Cancer were 39 % and 5 year survival rate was 13 %. In other words, scarce cancer can be said to be a highly malignant tumor which is expected to be quickly solved in current medical care even in the world.
One of the reasons why it is difficult to treat skills cancer is that early detection of pancreatic cancer and gastric cancer is difficult in the current clinical technique. Another reason for difficulty in treatment is that skill cancer has therapeutically resistant nature. This means that highly developed fibrous stroma (stroma) serves as a physical barrier for anticancer agent penetration and radiotherapy. This abundant cancer stroma causes biological interaction with cancer cells and promotes proliferation, infiltration and metastasis of cancer cells. The constituent main component of the cancer stroma is a cancer-related fibroblast (Cancer-associated fibroblast ; CAF), It is known that the important source (cell origin) of CAF is at least partially mesenchymal stem cells (Mesencymal stem cell ; MSC) that contaminate cancer tissue. Further, in pancreatic cancer or the like, development of blood vessels in abundant interstitial parts surrounding cancer cells is immature, and diffusion effect of anticancer agent in tumor tissue through blood vessels (Enhanced permeation and retention ; Since the EPR effect) cannot be sufficiently expected, the therapeutic effect in drug administration is low, and the control of the thickly developed cancer stroma has become a serious problem in the same type of cancer.
Incidentally, in recent years in the medical field in which peptides are utilized as biomaterials, attention has been paid to cell membrane-permeable (cell-absorbable) peptides such as Tat, Penetratin, poly-arginin and the like. However, these peptides are widely and non-selectively absorbed without distinction between normal cells or tissues and tumor cells or tumor tissues. Therefore, it is difficult to apply to DDS (Drug delivery system) tools for treatment of patient malignancies, including solid cancer, which require target-selective drug delivery, in view of causing serious side effects. In particular, a cell membrane-permeable (cell-absorbable) peptide such as Tat, which is widely used in experimental systems in the world, is known to have a property of causing accumulation in the liver, for example, see) Non-Patent Document 1.
On the other hand, cyclic RGD is the only medicated peptide. cyclic RGD targets αvβ3 integrin reported to be highly expressed in vascular endothelial cells (and some tumor cells) constituting a neovascular or existing blood vessel, and has an action point for enhancing vascular permeability. Therefore, (, for example, refer to Patent Document 1), which is applied as an imaging agent or DDS agent in a form of simultaneous combination with other medicines, instead of cyclic RGD alone. However, the permeability and action of cyclic RGD to the cancer cells themselves are very low, and are based on the diffusion effect of drugs through the blood vessels, and are a system which largely depends on the development and distribution) of tumor tissues of (blood vessels of the tumor tissue. From these results, it is impossible to expect a sufficient effect for anticancer therapy by direct killing of cancer cells themselves.
In order to solve the problems described above, the inventors have conventionally developed) peptides that act directly on pancreatic cancer cells or pancreatic cancer tissues and act directly on tumors by highly shifted absorbability (, see, for example,), Patent Document 2.
However, short-chain peptides that minimize absorption into normal cells and normal tissues and exhibit highly shifted absorbability into skills cancer tissues in which a large amount of CAF proliferates have not yet been developed.
|Scope of claims||
前記X 11及び前記X 12が同一のアミノ酸配列からなるペプチド残基である、請求項1～3のいずれか一項に記載のペプチド。
|IPC(International Patent Classification)||
National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN WS ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
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Contact Information for " PEPTIDE AND USE THEREOF "
- Niigata University (In Japanese)研究支援部産学連携課
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