Abstract: An object of the present invention is to provide a therapeutic strategy in the solid tumor area and a means useful therefor to further advance the clinical application of CAR therapy. There is prepared a gene-modified lymphocyte which expresses a chimeric antigen receptor having an EphrinB2 extracellular domain at the antigen recognition site.

Abstract: Provided is a method for preparing genetically-modified T cells expressing chimeric antigen receptor, comprising: (i) a step of preparing non-proliferative cells holding a viral peptide antigen, which are obtained by stimulating a group of cells comprising T cells using an anti-CD3 antibody and an anti-CD28 antibody followed by culturing in the presence of the viral peptide antigen and a treatment for causing the cells to lose their proliferation capability; (ii) a step of obtaining genetically-modified T cells into which a target antigen-specific chimeric antigen receptor gene has been introduced using a transposon method; (iii) a step of mixing the non-proliferative cells prepared by step (i) with the genetically-modified T cells obtained by step (ii), and co-culturing the mixed cells; and (iv) a step of collecting the cells after culture.

Abstract: In order to improve the efficiency of gene introduction in CAR therapy employing a transposon method, provided is a method for preparing genetically-modified T cells expressing chimeric antigen receptor, comprising: (1) a step of preparing non-proliferative cells which are obtained by stimulating a group of cells comprising T cells using an anti-CD3 antibody and an anti-CD28 antibody followed by a treatment for causing the cells to lose their proliferation capability; (2) a step of obtaining genetically-modified T cells into which a target antigen-specific chimeric antigen receptor gene has been introduced using a transposon method; (3) a step of mixing the non-proliferative cells prepared by step (1) with the genetically-modified T cells obtained by step (2), and co-culturing the mixed cells while stimulating the mixed cells using an anti-CD3 antibody and anti-CD28 antibody; and (4) a step of collecting the cells after culture.

Abstract: The present disclosure includes a method of producing a cell population containing Chimeric Antigen Receptor (CAR)-expressing immune cells, comprising co-culturing CAR-expressing immune cells and cells expressing a target antigen of the CAR, wherein the CAR-expressing immune cells are cells into which a CAR gene has been introduced and the target antigen-expressing cells are normal blood cells that have been engineered to express the target antigen.

Abstract: The present invention is intended to develop a chimeric antigen receptor (CAR) that is effective against solid tumor expressing anaplastic lymphoma kinase (ALK). The present invention provides a polynucleotide encoding a CAR protein comprising a target binding domain binding to an extracellular ligand binding region of ALK, a transmembrane domain, and an intracellular signaling domain. The target binding domain of the polynucleotide is selected from among FAM150A, FAM150B, and fragments thereof binding to the extracellular ligand binding region of ALK. The present invention also provides a genetically modified cell comprising the polynucleotide introduced thereinto.

Abstract: According to one embodiment, a composition is for delivering an objective substance to the T-cell malignant tumor cell. The composition contains a substance delivery carrier. The substance delivery carrier has a lipid particle, and the objective substance encapsulated in the lipid particle. The lipid particle contains, as constituents thereof, at least a first lipid represented by formula (I) and a second lipid represented by formula (II).

Abstract: An object of the present invention is to improve the efficiency of a method for producing chimeric antigen receptor (CAR)-expressing cells. The present invention provides a method for producing genetically modified mammalian cells, comprising the steps of: a) introducing a polynucleotide encoding a chimeric antigen receptor (CAR) protein to a cell population comprising T cells derived from a mammal by a transposon method to obtain a genetically modified cell population; b) providing an endogenous cell population derived from the mammal expressing a protein that binds to the CAR; and c) coculturing the genetically modified cell population of the step a) and the endogenous cell population of the step b).

Abstract: According to one embodiment, there is provided a method of producing a gene modification T cell (CAR-T cells) which expresses a chimeric antigen receptor (CAR). This method includes stimulating a cell population containing a T cell with an antibody which activates the T cell, bringing the cell population into contact with a nucleic acid-introducing carrier, wherein the nucleic acid-introducing carrier containing a lipid particle, a first nucleic acid and containing a CAR gene, and a second nucleic acid containing a transposase gene encapsulated in the lipid particle, and culturing the cell population after the contacting.

Abstract: It is intended to produce a cell expressing a mutant chimeric antigen receptor (CAR) having excellent cytotoxicity to target cells. The present invention provides a genetically modified cell having introduced thereinto a polynucleotide encoding a chimeric antigen receptor (CAR) protein having a target binding domain that specifically binds to a human granulocyte-macrophage colony stimulating factor (GM-CSF) receptor, a transmembrane domain, and an intracellular signaling domain, wherein the tar get binding domain is a mutant having the substitution of glutamic acid at position 21 in the amino acid sequence shown in SEQ ID NO: 1 with another amino acid.

Abstract: Production of a chimeric antigen receptor (CAR) expressing cell having excellent target cytotoxicity. Provided is a genetically modified cell comprising, introduced thereinto, a polynucleotide encoding a chimeric antigen receptor (CAR) protein having a target binding domain that specifically binds to a human granulocyte-macrophage colony stimulating factor (GM-CSF) receptor, a transmembrane domain and an intracellular signaling domain.

Abstract: An object of the present invention is to provide a therapeutic strategy in the solid tumor area and a means useful therefor to further advance the clinical application of CAR therapy. There is prepared a gene-modified lymphocyte which expresses a chimeric antigen receptor having an EphrinB2 extracellular domain at the antigen recognition site.

Abstract: Production of a chimeric antigen receptor (CAR) expressing cell having excellent target cytotoxicity. Provided is a genetically modified cell comprising, introduced thereinto, a polynucleotide encoding a chimeric antigen receptor (CAR) protein having a target binding domain that specifically binds to a human granulocyte-macrophage colony stimulating factor (GM-CSF) receptor, a transmembrane domain and an intracellular signaling domain.

Abstract: With the aim of improving the treatment result of CAR therapy, intended is to provide an effective means for the cytokine release syndrome, as an alternative to the administration of the anti-IL-6 receptor antibody or the like. Together with the target antigen-specific chimeric antigen receptor gene, a first nucleic acid construct which intracellularly producing an siRNA targeting interleukin-6 gene and/or a second nucleic acid construct which intracellularly producing an siRNA targeting tumor necrosis factor ? gene are introduced into the target cell, thus preparing the gene-modified lymphocyte expressing chimeric antigen receptor.

Abstract: In order to improve the efficiency of gene introduction in CAR therapy employing a transposon method, provided is a method for preparing genetically-modified T cells expressing chimeric antigen receptor, comprising: (1) a step of preparing non-proliferative cells which are obtained by stimulating a group of cells comprising T cells using an anti-CD3 antibody and an anti-CD28 antibody followed by a treatment for causing the cells to lose their proliferation capability; (2) a step of obtaining genetically-modified T cells into which a target antigen-specific chimeric antigen receptor gene has been introduced using a transposon method; (3) a step of mixing the non-proliferative cells prepared by step (1) with the genetically-modified T cells obtained by step (2), and co-culturing the mixed cells while stimulating the mixed cells using an anti-CD3 antibody and anti-CD28 antibody; and (4) a step of collecting the cells after culture.