公开(公告)号：KR100650384B1

公开(公告)日：2006-11-30

申请号：KR1020060070390

申请日：2006-07-26

Applicant: 전남대학교산학협력단 ,  주식회사 굿셀라이프

Inventor： 강형식 ,  김은미 ,  김상현 ,  윤지연 ,  고창보 ,  허영진 ,  심우영 ,  허성범 ,  이은희 ,  윤희정

IPC: C07K2/00

Abstract: A method for differentiating precursor natural killer cell into mature natural killer cell is provided to obtain large amount of the mature natural killer cell by treating the precursor natural killer cell with Axl receptor tyrosine kinase. The composition for inducing differentiation of precursor natural killer cell into mature natural killer cell is characterized in that it includes at least one ligand selected from the group consisting of antibody of Axl receptor tyrosine kinase(Axl), gamma-carboxylated growth-arrest specific gene6(Gas6) protein and protein S as a ligand of the Axl. The method comprises the steps of: (a) treating hematopoietic stem cell with interleukin-7, stem cell factor and Flt3 ligand to be differentiated into precursor natural killer cell; and (b) treating the precursor natural killer cell with at least one selected from the group consisting of antibody of Axl receptor tyrosine kinase(Axl), gamma-carboxylated growth-arrest specific gene6(Gas6) protein and protein S.

Abstract translation: 通过用Axl受体酪氨酸激酶处理前体天然杀伤细胞来提供将前体天然杀伤细胞分化为成熟天然杀伤细胞以获得大量成熟天然杀伤细胞的方法。 用于诱导前体天然杀伤细胞分化为成熟自然杀伤细胞的组合物的特征在于其包含至少一种选自Axl受体酪氨酸激酶抗体（Axl），γ-羧化生长抑制特异性基因6（ Gas6）蛋白和蛋白S作为Axl的配体。 该方法包括以下步骤：（a）用白细胞介素-7，干细胞因子和Flt3配体处理造血干细胞以分化成前体天然杀伤细胞; 和（b）用选自Axl受体酪氨酸激酶抗体（Axl），γ-羧化生长抑制特异性基因6（Gas6）蛋白质和蛋白质S中的至少一种处理前体天然杀伤细胞。

公开(公告)号：KR1020070030155A

公开(公告)日：2007-03-15

申请号：KR1020060109706

申请日：2006-11-07

Applicant: 전남대학교산학협력단 ,  주식회사 굿셀라이프

Inventor： 강형식 ,  김은미 ,  김상현 ,  윤지연 ,  고창보 ,  허영진 ,  심우영 ,  허성범 ,  이은희 ,  윤희정

IPC: C12N5/0783 ,  A61K35/17 ,  C12N9/12

CPC classification number: C12N5/0646 ,  A61K35/17 ,  C12N9/12

Abstract: A composition for differentiation of a mature natural killer(NK) cell and a method for production of the same mature natural killer cell are provided to produce a large quantity of mature natural killer cell to increase cancer-killing effects of the mature natural killer cell. The composition for differentiation of the mature natural killer cell from a precursor natural killer cell(pNK) comprises a ligand of Axl receptor tyrosine kinase. The method for producing the mature natural killer cell comprises the steps of: treating a hematopoietic stem cell with IL-7(interleukine 7), SCF(stem cell factor) and Flt3L(fms-related tyrosine kinase 3 ligand) to differentiate the hematopoietic stem cell into a precursor natural killer cell; and treating the precursor natural killer cell with the ligand of Axl receptor tyrosine kinase, wherein the mature killer cell is useful for treatment of cancers including large intestine cancer, breast cancer, non-Hodgikin's lymphoma and acute ymphocytic leukemia.

Abstract translation: 提供用于分化成熟天然杀伤（NK）细胞的组合物和用于生产相同成熟天然杀伤细胞的方法以产生大量的成熟天然杀伤细胞以增加成熟天然杀伤细胞的杀死癌症效果。 成熟天然杀伤细胞从前体天然杀伤细胞（pNK）分化的组合物包含Ax1受体酪氨酸激酶的配体。 用于生产成熟天然杀伤细胞的方法包括以下步骤：用IL-7（白细胞介素7），SCF（干细胞因子）和Flt3L（fms相关的酪氨酸激酶3配体）处理造血干细胞以分化造血干细胞 细胞成为前体天然杀伤细胞; 并用Ax1受体酪氨酸激酶的配体处理前体天然杀伤细胞，其中成熟的杀伤细胞可用于治疗包括大肠癌，乳腺癌，非霍奇金淋巴瘤和急性淋巴细胞性白血病的癌症。

公开(公告)号：KR1020070030114A

公开(公告)日：2007-03-15

申请号：KR1020060067483

申请日：2006-07-19

Applicant: 전남대학교산학협력단

Inventor： 강형식 ,  김은미 ,  이은희 ,  윤희정 ,  고창보

IPC: C12N5/07 ,  C12N15/63 ,  C12N15/06

Abstract: A method for production of natural killer(NK) cells is provided to treat cancers without side effects using the natural killer cells by using an Axl gene capable of promoting differentiation from hematopoietic stem cells into natural killer cells. The adult natural killer cells are produced by treating hematopoietic stem cells with IL-7(interleukine 7), SCF(stem cell factor) and Flt3L(fms-related tyrosine kinase 3 ligand), so as to differentiate them into NK precursor cells, and treating the NK precursor cells with the Axl gene, wherein the hematopoietic stem cells are isolated from human cord blood. A recombinant vector pLXSN-Axl contains the Axl gene. A transformant is produced by transforming a host cell, mouse RAW264.7 macrophage, with the recombinant vector pLXSN-Axl.

Abstract translation: 提供了一种生产天然杀伤（NK）细胞的方法，通过使用能促进从造血干细胞分化成自然杀伤细胞的Axl基因，使用天然杀伤细胞治疗无副作用的癌症。 通过用IL-7（白介素7），SCF（干细胞因子）和Flt3L（fms相关的酪氨酸激酶3配体）处理造血干细胞来产生成年自然杀伤细胞，以将它们分化成NK前体细胞，以及 用Axl基因处理NK前体细胞，其中从人脐血分离造血干细胞。 重组载体pLXSN-Ax1含有Axl基因。 通过用重组载体pLXSN-Ax1转化宿主细胞小鼠RAW264.7巨噬细胞来产生转化体。

公开(公告)号：KR1020070030115A

公开(公告)日：2007-03-15

申请号：KR1020060067485

申请日：2006-07-19

Applicant: 전남대학교산학협력단

Inventor： 강형식 ,  김은미 ,  이은희 ,  윤희정 ,  고창보

IPC: C12N5/07 ,  C12N5/071

Abstract: A method for production of a natural killer(NK) cell is provided to avoid side effects in cancer therapy by using a natural killer cell differentiated from a hematopoietic stem cell instead of a matured natural killer cell. The adult natural killer cell is produced by treating the hematopoietic stem cell with IL-7(interleukine 7), SCF(stem cell factor) and Flt3L(fms-related tyrosine kinase 3 ligand) to differentiate the hematopoietic stem cell into a NK precursor cell, and treating the NK precursor cell with the Axl receptor and its ligand Gas6. The hematopoietic stem cell is isolated from the human cord blood; the Axl is a recombinant Axl produced from a transformant containing a recombinant vector pLXSN-Axl; the host cell of the transformant containing the recombinant vector pLXSN-Axl is a mouse RAW264.7 macrophage; the recombinant Gas6 is produced from a transformant containing a recombinant vector pcDNA3.1(+)-GAS6; and the host cell of the transformant containing the recombinant vector pcDNA3.1(+)-GAS6 is a mouse OP9 cell line.

Abstract translation: 提供了一种生产自然杀伤（NK）细胞的方法，以通过使用从造血干细胞分化而不是成熟的天然杀伤细胞分化的天然杀伤细胞来避免癌症治疗中的副作用。 通过用IL-7（白细胞介素7），SCF（干细胞因子）和Flt3L（fms相关的酪氨酸激酶3配体）处理造血干细胞以将造血干细胞分化成NK前体细胞来产生成年自然杀伤细胞 ，并用Ax1受体及其配体Gas6处理NK前体细胞。 造血干细胞从人脐带血中分离出来; Ax1是由含有重组载体pLXSN-Ax1的转化体产生的重组Ax1; 含有重组载体pLXSN-Ax1的转化体的宿主细胞是小鼠RAW264.7巨噬细胞; 重组Gas6由含有重组载体pcDNA3.1（+）-GAS6的转化体产生; 含有重组载体pcDNA3.1（+） - GAS6的转化体的宿主细胞是小鼠OP9细胞系。

公开(公告)号：KR1020080008060A

公开(公告)日：2008-01-23

申请号：KR1020060067484

申请日：2006-07-19

Applicant: 전남대학교산학협력단

Inventor： 강형식 ,  김은미 ,  이은희 ,  윤희정 ,  고창보

IPC: C12N5/07 ,  C12N15/63 ,  C12N15/06

Abstract: A method for preparing a natural killer cell is provided to treat cancer by obtaining the adult natural killer cell from an adult stem cell. A method for preparing a natural killer cell comprises the steps of: (a) treating an adult stem cell derived from cord blood of human with IL-7, SCF and Flt3L to be differentiated into a natural killer precursor cell; and (b) treating the natural killer precursor cell with Gas6. A transfectant comprises a recombinant vector pcDNA3.1(+)-GAS6.

Abstract translation: 提供一种制备自然杀伤细胞的方法，通过从成体干细胞获得成年自然杀伤细胞来治疗癌症。 制备天然杀伤细胞的方法包括以下步骤：（a）用IL-7，SCF和Flt3L处理源自人脐血的成体干细胞以分化为天然杀伤细胞前体细胞; 和（b）用Gas6处理天然杀伤前体细胞。 转染子包含重组载体pcDNA3.1（+）-GAS6。

公开(公告)号：KR1020060135280A

公开(公告)日：2006-12-29

申请号：KR1020050055143

申请日：2005-06-24

Applicant: 전남대학교산학협력단

Inventor： 강형식 ,  김은미 ,  이은희 ,  윤희정 ,  고창보

IPC: C12N15/867

Abstract: Novel recombinant vectors are provided to be used for expressing triggering receptor expressed on myeloid cells 2b(TREM-2) which is expressed at the activity of natural killer cell and the differentiation process and plays important role on innate immunity. The recombinant vector pcDNA3.1-TREM-2 expresses TREM-2 involved with innate immunity. The recombinant vector pLXSN-TREM-2 expresses TREM-2 involved with innate immunity.

Abstract translation: 提供新的重组载体用于表达在骨髓细胞2b（TREM-2）上表达的触发受体，其以天然杀伤细胞的活性和分化过程表达，并对先天免疫起重要作用。 重组载体pcDNA3.1-TREM-2表达涉及先天免疫的TREM-2。 重组载体pLXSN-TREM-2表达涉及先天免疫的TREM-2。