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IMMUNOCOMPETENT CELL AND EXPRESSION VECTOR EXPRESSING REGULATORY FACTORS OF IMMUNE FUNCTION

外国特許コード F170009266
整理番号 (S2016-0507-N0)
掲載日 2017年10月24日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2017JP010437
国際公開番号 WO 2017159736
国際出願日 平成29年3月15日(2017.3.15)
国際公開日 平成29年9月21日(2017.9.21)
優先権データ
  • 特願2016-053913 (2016.3.17) JP
発明の名称 (英語) IMMUNOCOMPETENT CELL AND EXPRESSION VECTOR EXPRESSING REGULATORY FACTORS OF IMMUNE FUNCTION
発明の概要(英語) The present invention addresses the problem of providing: an immunocompetent cell in which regulatory factors of immune function from immunocompetent cells are expressed in the immunocompetent cell, and which combines proliferative capacity, viability, and a capacity for T-cell accumulation; and an immune function regulatory factor expression vector for preparing said immunocompetent cell. An immunocompetent cell is prepared which expresses interleukin 7 (IL-7), CCL19, and a cell surface molecule for specifically recognizing cancer antigens. The cell surface molecule for specifically recognizing cancer antigens is preferably a T-cell receptor that specifically recognizes cancer antigens, and the immunocompetent cell is preferably a T-cell.
従来技術、競合技術の概要(英語) BACKGROUND ART
Many cancer worldwide disease of affected individuals and, in general chemotherapy, radiation therapy, or surgical therapy has been widely conducted. However, side effects from being created, or may be part of the functions of lost, such as treats metastasis would be difficult to, various problems.
Therefore, in order to maintain high QOL of patients more, in recent years, has been the development of immunotherapy. In this immune therapy, immune cell therapy, the immune cells were harvested from the patient, such as enhancing immune function of the immune system were treated and amplified, therapy is again introduced into the patient. Specifically, T cells were harvested from the patient, such T cells by introducing a gene encoding CAR is amplified, again introduced into the patient therapy (see non-patent document 1) have been known. This therapy is, worldwide clinical trials has progressed, such as a hematopoietic malignancy such as leukemia and lymphoma shows efficacy in a result is obtained.
In addition, the immune function of the immune system of cells or the like T control factors include, cytokines, chemokines, signal control protein or the like, at least several hundred one type of agent has been known. Interleukin 7 (IL-7) in which is essential to the survival of cytokine T cells, bone marrow, thymus, lymphoid organs, such as stromal tissue of non-hematopoietic cells produced by the known. Of such IL-7 T cell function is utilized, alpha IL-7 and fuzed IL-7R T cells that express the receptor (see Patent Document 1) is disclosed. However, such T receptors in a cell, one as a fusion protein, limited to the surface of the membrane of a cell introduced T expressed, only to the ligand-independent activation of self-cells such as cytokine IL-7R to only to the transfer, the receptor was not introduced into the T cells has not been possible to enhance the ability of.
In addition, CCL19 or CCL21, where reduced expression of the alpha IL-7 SIRP in the spleen T cell region in the mutant mice may result in a maintenance deficient (see non-patent document 2) or, CCL19 and CCL21, the secondary lymphoid tissue IL-7 (spleen or lymph nodes) and function to maintain cellular homeostasis in T has (see non-patent document 3) is disclosed. However, the non-patent document 2, the secondary lymphoid tissues T 3 constitutively present cell regions a non-activated T cells and showing a behavior of the same, directly related to the anti-tumor immune response was not those that exhibit a. Further, the non-patent document 2, CCL19 or CCL21 in 3, IL-7 expressing cells but not on T, secondary lymphoid tissue present in the cells in the reticuloendothelial system.
On the other hand, T-cell receptor (T cell receptor: hereinafter, also referred to as' TCR ') is expressed on the cell membrane of the T and antigen receptor molecule. Alpha chain and beta chain, gamma chain and delta chain or as a heterodimer are present, major histocompatibility complex (MHC) antigen molecules attached to a molecule recognizing the activated T cells known.
The function of such TCR is applied, a cancer cell expressing TCR recognize tumor antigens can be obtained from a cancer patient T gene introduced into a cell, introduced into the patient again after amplification has been the development of immunotherapy. More specifically, to specifically recognize WT1-expressing cells containing cells expressing TCR for the treatment of meningioma (see Patent Document 2) is disclosed.
Is formed on a part of the foregoing techniques, the anti-tumor effect of a hematological malignancy but the admission, the solid cancer is still in the example shown there is no significant effect. This is the immune system in vivo transfected with a low efficiency of viable, transfected or induced by the immune system of the endogenous immune system activation and, insufficient accumulation at the local tumor is considered to be a problem, development of techniques for solving these has been demanded.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • YAMAGUCHI UNIVERSITY
  • 発明者(英語)
  • TAMADA, Koji
  • SAKODA, Yukimi
  • ADACHI, Keishi
国際特許分類(IPC)
指定国 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 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 SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN 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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