Methods of expanding tumor infiltrating lymphocytes (TILs) using a potassium channel agonist, such as a K.sub.Ca3.1 (IK channel) agonist, and uses of such expanded TILs in the treatment of diseases such as cancer are disclosed herein.

A molecule capable of binding to human 4-1BB includes the amino acid sequences of HCDR1, HCDR2 and HCDR3 in the heavy chain variable region of the antibody provided by present invention are shown sequentially at positions 31-35, positions 50-64, and positions 98-106 in SEQ ID No.1 from the N-terminus. The amino acid sequences of LCDR1, LCDR2 and LHCDR3 in the light chain variable region are shown sequentially at positions 24-34, positions 50-56, and positions 89-97 in SEQ ID No.2 from the N-terminus. The antibodies provided by the present invention can bind to human and monkey 4-1BB, exhibit high affinity to human 4-1BB and effectively enhance T cell responses; they can be used to regulate the immune responses mediated by T cells and antibodies; as immune modulators, they have a wide range of therapeutic uses in diseases such as cancer, autoimmune diseases, inflammatory diseases, and infectious diseases, etc.

There is provided herein a method for expanding human CD4-CD8- regulatory T cells (DN Tregs) from a population of cells comprising DN Tregs, comprising: culturing the population of cells with artificial antigen presenting cells (APCs), preferably the DN Tregs are αβ-TCR-CD56- or alternatively γ8-TCR+.

Disclosed is a chimeric antigen receptor with improved persistency.

Provided herein are methods of activating immune cells. The method includes providing a population of immune cells and contacting the population of immune cells with a first agent and a second agent. The first agent includes an immune cell activator attached to a first binder moiety, and the second agent includes at least one capture oligomer. The at least one capture oligomer is capable of associating with the first binder moiety. Also provided are kits for activating immune cells.

Disclosed herein are methods and compositions for inactivating TCR and/or HLA genes, using engineered nucleases comprising at least one DNA binding domain and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided.

The present invention aims to solve a problem in T-cell transfer therapy and the like, which is T-cell exhaustion, and to provide a technique to enhance T cell activity. T cells having cell surface markers of CD45RA.sup.+ and CCR7.sup.+ can be produced by culturing activated T cells in the presence of (a) a conditioned medium derived from stromal cells or (b) CXCL12.

The invention relates to: a composition for culturing natural killer cells, comprising, as an active ingredient, a fusion protein comprising an IL-2 protein and a CD80 protein; and a method for preparing natural killer cells by using same. Particularly, a composition for culturing natural killer cells, comprising, as an active ingredient, a fusion protein comprising IL-2 or a variant thereof and CD80 or a fragment thereof, of the present invention; promotes the proliferation of natural killer cells, induces the expression of CD16 and NKp46, and increases the expression and secretion of granzyme B and perforin, thereby being effectively usable in the preparation of natural killer cells having an excellent anticancer immune function.

The disclosure relates to immune cells for use in adoptive cell therapy that express an inhibitory receptor, useful for treating a disease or disorder, for example, cancer. The disclosure provides immune cells with reduced or eliminated HLA expression, that express an inhibitory receptor, methods of making same, shRNAs targeting HLA-A mRNA, and polynucleotides and vectors encoding same.

Provided by the disclosure are compositions and methods for modulating differentiation of regulatory T cells. In some embodiments, methods include selectively decreasing IL-23R activity and/or IL-23R expression without significantly decreasing IL-12RP activity and/or IL-12RP expression.