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.

Provided by the disclosure are methods for modulating differentiation of regulatory T cells (e.g., CD4.sup.+ or CD8.sup.+ regulatory T cells). In some embodiments, methods include contacting regulatory T cells with an agent that decreases Helios activity and/or Helios expression.

The disclosure provides immunogenic cells expressing LMP1, and use thereof in activating T cells and treating cancer. Also provided are methods of producing the immunogenic cells.

Provided herein are single-chain and multi-chain chimeric antigen receptors, nucleic acids encoding the same, and mammalian cells expressing the same. Also provided are methods of treating a cancer in a subject using a mammalian cell expressing any of these single-chain and multi-chain chimeric antigen receptors.

Methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject, the method comprising a step of administering a recombinant hGM-CSF antagonist to the subject, wherein said administering inhibits or reduces the incidence or the severity of immunotherapy-related toxicity in said subject, are provided. An hGM-CSF antagonist for use in methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject also are provided.

Antigen binding molecules, chimeric receptors, and engineered immune cells to FLT3 are disclosed in accordance with the invention. The invention further relates to vectors, compositions, and methods of treatment and/or detection using the FLT3 antigen binding molecules and engineered immune cells.

The present disclosure provides methods of hematopoietic stem cell transplantation (HSCT). In particular, the present disclosure provides a method of HSCT using a combination of an in-vivo T-cell depletion method, with an ex-vivo method of ?? T cell expansion and ?? T cell depletion. The in-vivo T-cell depletion method depletes (in-vivo) the alloreactive T cells that would otherwise increase the risk of GvHD.

Provided are methods, compositions, recombinant DNA molecules, and kits for cloning T cell receptors (TCRs). The methods facilitate construction of TCR expression libraries from biological samples containing antigen-specific T cells, including but not limited to tumor biopsies, including frozen tumor biopsies. Peripheral T cells that were engineered with library-derived TCR genes show potent therapeutic anti-tumor effects. The method can be performed using any sample that contains T cells, and can be performed with oligoclonal populations of T cells, such as T cells that have infiltrated a tumor. Primer combinations for first strand cDNA synthesis, second strand cDNA synthesis, and for cloning a plurality of distinct TCR ? and TCR ? chains into a plurality of vectors are provided. Cells containing the vectors are provided, as are kits for use in rapid cloning of the TCR ? and TCR ? chains.

A method for treating inflammation and/or autoimmune diseases comprises administering to a subject in need thereof, a composition comprising a CDK8 inhibitor. In another aspect, a method for increasing IL-10 production comprises administering to a subject in need thereof a CDK8 inhibitor. In another aspect, a method for enhancing T.sub.reg cell differentiation, comprising administering a composition comprising a CDK8 inhibitor. In certain example embodiments, the subject suffers from an inflammatory bowel disease. In certain other example embodiments, the subject requires immunosuppression to prevent rejection following a transplantation procedure.

Embodiments of the disclosure include methods and compositions for enhancing expansion of immune cells for immunotherapy. In particular embodiments, immune cells, such as T-cells, express a constitutively active cytokine receptor in which the transmembrane and endodomains are able to provide an activating signal separately from any input to the corresponding exodomain to which they are operably linked. In specific embodiments, the transmembrane and endodomain from IL-7R? is utilized with the exodomain of CD34.