A method of generating a CD4.sup.+FoxP3.sup.+ Treg cell, the method includes administering at least one complement antagonist to a naive CD4.sup.+T cell at an amount effective to substantially inhibits C3a receptor (C3aR) and/or C5a receptor (C5aR) signal transduction in the CD4.sup.+ T cell, induce TGF-?1 expression of the CD4.sup.+ T cell, and induce differentiation of the of the naive CD4.sup.+ T cell into a CD4.sup.+FoxP3.sup.+ Treg cell.

A method of treating cancer in a subject includes contacting an enriched population of T-cells obtained from cancer or tumor draining lymph nodes ex-vivo with: an anti-CD3 antibody, an anti-CD28 antibody, and/or functional fragments thereof, and optionally a VEGF inhibitor and/or an IL-2 receptor agonist, at amounts effective to activate and expand the T-cells and administering the activated and expanded T-cells to the subject.

The purpose of the present invention is to produce a chimeric antigen receptor (CAR) specific to glypican-1 (GPC-1) and to treat squamous cell carcinoma with genetically modified cells capable of expressing the CAR. The present invention provides: a chimeric antigen receptor for use in the treatment and/or prevention of squamous cell carcinoma, said chimeric antigen receptor comprising an extracellular domain capable of binding to GPC-1, a transmembrane domain and one or multiple intracellular domains, wherein at least one of the intracellular domains is an intracellular domain containing a primary cytosolic signaling sequence or an intracellular domain containing both a primary cytosolic signaling sequence and a secondary cytosolic signaling sequence; a genetically modified cell capable of expressing the chimeric antigen receptor; and a cell preparation containing the cell.

The present invention relates to a formulation comprising an inhibitor of NFAT activation for use in treating or preventing undesirable effects, more particularly undesirable effects occurring in conjunction with T cell-mediated therapies. The undesirable effects may be cytokine release syndrome (CRS) or symptoms associated with gastrointestinal (GI) inflammation, for example associated with inflammatory bowel diseases, such as ulcerative colitis, optionally caused by activated T cell activity. In addition to ameliorating undesirable effects, the invention is aimed at also maintaining the therapeutic effects of the T-cell mediated therapy.

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., multiple myeloma). It relates to anti-CD56 antibodies, chimeric antigen receptors (CARs) that specifically target human CD56, and immunoresponsive cells comprising such CARs. The presently disclosed CD56-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

Provided is an active ingredient of a pharmaceutical composition for treating myeloma. Specifically, provided is an antibody whose epitope is present in the region of the amino acid residue positions 20 to 109 of human integrin ?.sub.7.

The present invention provides methods for increasing expression of at least one co-stimulatory and/or co-inhibitory receptor on a T cell comprising contacting said T cell with an anti-CTLA4 antibody. In one aspect the co-stimulatory and/or co-inhibitory receptor is selected from the group of: PD-1, OX40, ICOS, CD137, TIM3, and LAG3. The present invention also provides methods of treating cancer in a human in need thereof comprising administering an anti-CTLA antibody and at least one additional agent directed to at least one co-stimulatory and/or co-inhibitory receptor to said human. In one aspect, the agent is directed to at least one co-stimulatory and/or co-inhibitory receptor selected from the group of: PD-1, OX40, ICOS, CD137 (4-1BB), TIM3, and LAG3.

The invention provides antibodies, and antigen-binding fragments thereof, that specifically bind to a polypeptide, or antigenic portion thereof, wherein the polypeptide is selected from a) MUC16 ectodomain polypeptide, b) MUC16 cytoplasmic domain polypeptide, and c) MUC16 extracellular domain polypeptide that contains a cysteine loop polypeptide. The invention's antibodies and compositions containing them are useful in diagnostic and therapeutic applications for diseases in which MUC16 is overexpressed, such as cancer.

The present invention provides compositions and methods for treating KMA-expressing malignancies including chimeric antigen receptors (CARs) and T cells containing CARs (CAR T-cells). The invention also provides methods and compositions comprising CAR T-cells co-expressing other anti-tumoral agents including cytokines and antibodies.

This invention relates to the field of therapeutics. Most specifically invention provides methods of generating in vitro engineered immune cells conditionally expressing interleukin-12 (IL-12) and one or more immunomodulators under the control of a gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals.