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IMMUNOCOMPETENT CELL AND EXPRESSION VECTOR EXPRESSING REGULATORY FACTORS OF IMMUNE FUNCTION

Foreign code F170009266
File No. (S2016-0507-N0)
Posted date Oct 24, 2017
Country WIPO
International application number 2017JP010437
International publication number WO 2017159736
Date of international filing Mar 15, 2017
Date of international publication Sep 21, 2017
Priority data
  • P2016-053913 (Mar 17, 2016) JP
Title IMMUNOCOMPETENT CELL AND EXPRESSION VECTOR EXPRESSING REGULATORY FACTORS OF IMMUNE FUNCTION
Abstract 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.
Outline of related art and contending technology 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.
Scope of claims (In Japanese)[請求項1]
がん抗原を特異的に認識する細胞表面分子、インターロイキン7(IL-7)、及びCCL19を発現する免疫担当細胞。
[請求項2]
がん抗原を特異的に認識する細胞表面分子が、がん抗原を特異的に認識するT細胞受容体であることを特徴とする請求項1記載の免疫担当細胞。
[請求項3]
免疫担当細胞がT細胞であることを特徴とする請求項1又は2記載の免疫担当細胞。
[請求項4]
がん抗原が、WT1、MART-1、NY-ESO-1、MAGE-A1、MAGE-A3、MAGE-A4、Glypican-3、KIF20A、Survivin、AFP-1、gp100、MUC1、PAP-10、PAP-5、TRP2-1、SART-1、VEGFR1、VEGFR2、NEIL3、MPHOSPH1、DEPDC1、FOXM1、CDH3、TTK、TOMM34、URLC10、KOC1、UBE2T、TOPK、ECT2、MESOTHELIN、NKG2D、P1A、GD2、又はGM2であることを特徴とする請求項1~3のいずれか1項に記載の免疫担当細胞。
[請求項5]
請求項1~4のいずれか1項に記載の免疫担当細胞を作製するための以下の(a)~(e)のいずれかの発現ベクター。
(a)がん抗原を特異的に認識する細胞表面分子をコードする核酸、IL-7をコードする核酸、及びCCL19をコードする核酸を含有する発現ベクター:
(b)以下の(b-1)及び(b-2)の2つの発現ベクター:
(b-1)がん抗原を特異的に認識する細胞表面分子をコードする核酸を含有する発現ベクター;
(b-2)IL-7をコードする核酸、及びCCL19をコードする核酸を含有する発現ベクター;
(c)以下の(c-1)及び(c-2)の2つの発現ベクター:
(c-1)がん抗原を特異的に認識する細胞表面分子をコードする核酸、及びIL-7をコードする核酸を含有する発現ベクター;
(c-2)CCL19をコードする核酸を含有する発現ベクター;
(d)以下の(d-1)及び(d-2)の2つの発現ベクター:
(d-1)IL-7をコードする核酸を含有する発現ベクター;
(d-2)がん抗原を特異的に認識する細胞表面分子をコードする核酸、及びCCL19をコードする核酸を含有する発現ベクター;
(e)以下の(e-1)、(e-2)及び(e-3)の3つの発現ベクター:
(e-1)がん抗原を特異的に認識する細胞表面分子をコードする核酸を含有する発現ベクター;
(e-2)IL-7をコードする核酸を含有する発現ベクター;
(e-3)CCL19をコードする核酸を含有する発現ベクター;
[請求項6]
がん抗原を特異的に認識する細胞表面分子が、がん抗原を特異的に認識するT細胞受容体であることを特徴とする請求項5記載の発現ベクター。
[請求項7]
(a)の発現ベクターにおける、がん抗原を特異的に認識する細胞表面分子をコードする核酸、IL-7をコードする核酸、及び、CCL19をコードする核酸、
(b-2)の発現ベクターにおける、IL-7をコードする核酸、及びCCL19をコードする核酸、
(c-1)の発現ベクターにおける、がん抗原を特異的に認識する細胞表面分子をコードする核酸、及びIL-7をコードする核酸、又は
(d-2)の発現ベクターにおける、がん抗原を特異的に認識する細胞表面分子をコードする核酸、及びCCL19をコードする核酸、
が自己切断型ペプチドを介して連結されていることを特徴とする請求項5又は6記載の発現ベクター。
[請求項8]
自殺遺伝子をコードする核酸を含有することを特徴とする請求項5~7のいずれか1項に記載の発現ベクター。
[請求項9]
請求項1~4のいずれか1項に記載の免疫担当細胞と、薬学的に許容される添加剤とを含有する抗がん剤。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • YAMAGUCHI UNIVERSITY
  • Inventor
  • TAMADA, Koji
  • SAKODA, Yukimi
  • ADACHI, Keishi
IPC(International Patent Classification)
Specified countries 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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