A kit for use in adding to a cultural medium for culturing natural killer (NK) cells includes a B unit including a basic solution including IL-2, L-glutamine dissolved in a cell culture medium, a C1 unit including of a cytokine 1 solution including IL-12 and IL-18 dissolved in the basic solution, a C2 unit including of a cytokine 2 solution including IL-15 dissolved in the basic solution, an A1 unit including of an antibody 1 solution including an anti-CD16 antibody and an anti-CD56 antibody dissolved in the basic solution, an A2 unit including of an antibody 2 solution including the antibody 1 solution and the basic solution in a volume ratio of 1:6-10, and a D unit including of an antibody-cytokine mixed solution including an anti-CD3 antibody dissolved in the cytokine 1 solution.

Provided is a method for inducing T cells for a cell-based immunotherapy, comprising the steps of: (1) providing Rag 1 and/or Rag 2 gene knockout human pluripotent stem cells bearing genes encoding a T cell receptor specific for a desired antigen, and (2) inducing T cells from the pluripotent stem cells of step (1). Further provided are a cell-based immunotherapy method that uses the T cells for the cell-based immunotherapy and an iPS cell bank for the cell-based immunotherapy.

The present disclosure relates to compositions and methods for enhancing cell response and/or expanding chimeric antigen receptor (CAR) cells and/or maintenance in vivo and/or in vitro. In embodiments, the method comprises obtaining CAR T cells comprising a CAR comprising a binding domain that binds a solid tumor antigen, a transmembrane domain, and an intracellular domain; and contacting the CART cells with white blood cells and a bispecific antibody, such as a Bispecific T cell engager (BiTE®), thereby activating the CAR T cells, wherein the level of activation of the CAR T cells is higher than the level of activation of CAR T ells that are contacted with B cells without the bispecific antibody. The bispecific antibody comprises a first binding domain binding CD3 and a second binding domain binding CD19, CD20, CD22, or BCMA.

Provided herein is a family of programmable de novo designed transmembranal protein domain polypeptides, and uses thereof in the production of engineered chimeric antigen receptor T (CAR T) cells, which are used, for example, to fight cancer.

The present invention relates to methods for developing engineered T-cells for immunotherapy that are non-alloreactive. The present invention relates to methods for modifying T-cells by inactivating both genes encoding T-cell receptor and an immune checkpoint gene to unleash the potential of the immune response. This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.

A method of expanding TCRalpha deficient T-cells by expressing pTalpha or functional variants thereof into said cells, thereby restoring a functional CD3 complex. This method is particularly useful to enhance the efficiency of immunotherapy using primary T-cells from donors. This method involves the use of pTalpha or functional variants thereof and polynucleotides encoding such polypeptides to expand TCRalpha deficient T-cells. Such engineered cells can be obtained by using specific rare-cutting endonuclease, preferably TALE-nucleases. The use of Chimeric Antigen Receptor (CAR), especially multi-chain CAR, in such engineered cells to target malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.

The present invention includes compositions and methods for modifying a T cell with a nucleic acid encoding a switch molecule comprising an extracellular domain comprising a membrane receptor or fragment thereof and an intracellular domain comprising a signaling receptor or fragment thereof. In one aspect, a method comprises introducing a nucleic acid encoding a switch molecule and a nucleic acid encoding a soluble fusion protein and/or a nucleic acid encoding a bispecific antibody into a population of cells comprising T cells, wherein the T cells transiently expresses the switch molecule and soluble fusion protein or bispecific antibody. In other aspect, compositions of T cells and methods of treating a disease or condition, such as cancer or an autoimmune disease, are also included.

The invention provides improved T cell compositions and methods for manufacturing T cells. More particularly, the invention provides methods of T cell manufacturing that result in adoptive T cell immunotherapies with improved survival, expansion, and persistence in vivo.

The present invention provides a nucleic acid molecule encoding a specific binding molecule capable of binding an h TERT peptide comprising the amino acid sequence set forth in SEQ ID NO: 1 when the peptide is presented by a Class II Major Histocompatibility Complex (MHC), wherein the specific binding molecule comprises a first polypeptide comprising a variable region of an α-chain and a second polypeptide comprising a variable region of a β-chain of a T-cell receptor (TCR), and wherein: (a) the variable region of an α-chain comprises CDR sequences CDR1, CDR2 and CDR3 which respectively comprise the amino acid sequences set forth in SEQ ID NOs: 2, 3 and 4; and (b) the variable region of a β-chain comprises CDR sequences CDR1, CDR2 and CDR3 which respectively comprise the sequences set forth in SEQ ID NOs: 5, 6 and 7. Recombinant constructs, vectors and host cells comprising such nucleic acid molecules are also provided, as are specific binding molecules encoded by such nucleic acid molecules. The present invention has utility in the treatment of cancer.

This disclosure relates to improving CAR-T expansion and/or survival using CD-3 antibodies alone or in combination with other co-stimulatory molecules such as an anti-IL-6 receptor monoclonal antibody, an anti-CD28 monoclonal antibody, an IL-17 monoclonal antibody or specific inhibitors of signaling pathways of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), or mammalian target of rapamycin (mTOR).