This invention relates, inter alia, to compositions of low serum or serum free media and methods for the expansion of T cell populations and methods for using such populations of cells. In some aspects, the invention relates to compositions and methods for the selective expansion of T cell subpopulations.

Provided in the present invention are a specific antibody of BCMA and a BCMA-targeting immune effector cell, and also provided are a chimeric antigen receptor-modified T cell prepared using the antibody and the use thereof.

The present disclosure relates to methods for using BCMA-specific binding molecules (such as a BCMA-specific chimeric antigen receptor or antibody) in combination with -secretase inhibitors, which can be done concurrently or sequentially, to treat or prevent a B-cell related proliferative disease, such as a cancer or autoimmune disease, or the like. A BCMA-specific binding molecule in combination with -secretase inhibitor can be used in, for example, adoptive immunotherapy.

The present invention provides a cell comprising first and second chimeric antigen receptors (CARs), which bind to different antigens, wherein the first CAR binds to Transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). The present invention also provides a cell comprising a tan CAR comprising first and second antigen-binding domains which bind to different antigens, wherein the first antigen binding domain binds the antigen Transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). The present invention further provides corresponding nucleic acid sequences and/or constructs, kits and vectors comprising said nucleic acid sequences and/or constructs, molecules and methods for making such cells. The cells may be used in cellular immunotherapy approaches for treating diseases such as multiple myeloma.

Disclosed are CAR polypeptides comprising a target specific receptor and a death domain. Disclosed are CAR polypeptides comprising a LINGO1 antigen binding domain, a transmembrane domain, and an intracellular signaling domain. Disclosed are CAR cells comprising one or more of the disclosed CAR polypeptides. Disclosed are cells comprising an altered ?4?1 integrin. Disclosed are methods of treating comprising administering one or more of the disclosed cells to a subject in need thereof.

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 disclosure relates to the in vivo prevention or treatment of hematologic malignancy relapse using a TNFR2 antagonist (an anti TNFR2 antagonist antibody) (i) for use in the prevention or treatment of hematologic malignancy relapse after allogeneic hematopoietic stem cell transplantation (AHCT) or after a treatment with lymphocytes and (ii) for use in enhancing the graft-versus-leukemia-activity (GVL activity) of a hematopoietic stem cell transplantation (HCT) or a treatment with lymphocytes.

Described herein are methods for producing and utilizing an alternative signal 1 domain to construct an optimally signaling CAR. Alternative signal 1 domains of the present technology are based on alternatives to CD3, including mutated ITAMs from CD3 (which contains 3 IT AM motifs), truncations of CD3, and alternative splice variants known as CD3s, CD3 theta, and artificial constructs engineered to express fusions between CD3s or CD30 and CD3. CAR polypeptides comprising alternative signal 1 domains are utilized to engineer CAR T cells. Further, this technology related to methods of treating cancer by administering to a subject in need thereof CAR T cells comprising alternative signal 1 domains.

Natural Killer (NK) cells and NK cell lines are modified to increase cytotoxicity, wherein the cells and compositions thereof have a use in the treatment of cancer. Modified NK cells and NK cell lines are produced via genetic modification of CD38.sup.low NK cells to transiently express the Fc receptor CD16 (F158V) from mRNA introduced into the NK cell, rather than from a chromosomal coding sequence. The cytotoxicity of the modified NK cells against CD38-expressing cancer cells is increased by administration of these modified cells in combination with a CD38-binding antibody. Separately, cytotoxicity against breast cancer is exhibited by the modified NK cells in combination with

Herceptin.

An object of the present invention is to provide CAR-expressing T cells that coexpress a chimeric antigen receptor (CAR) and a T cell immune function-enhancing factor and have a high immunity-inducing effect and antitumor activity, and to provide a CAR expression vector for the preparation of the CAR-expressing T cells.

A CAR expression vector comprises a nucleic acid encoding a chimeric antigen receptor (CAR) and a nucleic acid encoding a T cell immune function-enhancing factor, wherein the nucleic acid encoding an immune function-enhancing factor is a nucleic acid encoding interleukin-7 and a nucleic acid encoding CCL19, a nucleic acid encoding a dominant negative mutant of SHP-1, or a nucleic acid encoding a dominant negative mutant of SHP-2, or a CAR-expressing T cell introduced with the CAR expression vector are prepared.