An in vitro expansion process for rapid expansion of antigen specific T cells, such as allogeneic antigen specific T cells comprising the steps culturing in a gas permeable vessel a population of PBMCs (such as allogeneic PBMCs) in the presence of antigen, for example a peptide or peptide mix relevant to a target antigen(s), in the presence of an exogenous cytokine characterized in that the expansion to provide the desired population of T cells is 14 days or less, for example 9, 10, 11 or 12 days, such as 10 days. The disclosure also extends to T cell populations generated by and obtained from the method and the use of same in therapy.

Novel MSC stem-cell culture and therapy methods and culture medium compositions for the purpose of inducing, activating, or priming discrete uniform cell phenotypes to selectively promote or suppress inflammation and immunity, yielding polarized, primed, activated, or induced cells used in cell-based therapy.

The present invention provides an isolated cell composition suitable for adoptive immunotherapy, as well as methods of manufacturing the cell compositions and methods of treatment with the cell compositions. The composition comprises, in a pharmaceutically acceptable carrier, at least about 10.sup.6 CD8+ T cells specific for target peptide antigen(s). In various embodiments, the composition is predominately CD8+ T cells, and at least about 20% of T cells in the composition exhibit a central or effector memory phenotype, providing for a robust and durable adoptive therapy from a natural T cell repertoire that has undergone natural selection.

The present disclosure provides compositions comprising mature dendritic cells loaded with autologous tumor cell lysates for the treatment of liver cancers, such as hepatocellular carcinoma. Hepatocellular carcinoma (HCC) is the fifth leading cancer and third leading cause of cancer-related mortality worldwide. Surgical resection and liver transplantation remain the mainstay of effective therapy for patients with early disease. However, a prevalent problem with HCC is the high likelihood of initial diagnosis at an advanced stage.

This disclosure relates to methods and compositions for addressing conditions of dysbiosis and/or inflammation, such as enteropathy, associated with administration of non-steroidal anti-inflammatory drug (NSAID). The disclosure includes methods comprising administering an effective amount of a tryptophan derived microbiota metabolite (TDMM) to a subject that has also been administered, or is expected to have administered, a NSAID.

Disclosed herein is a different and novel approach to cancer vaccines using a subject's own dendritic cells (DCs) and macrophages (Mphs) in combination to present cancer antigens to the immune system. Further disclosed are methods of producing monocyte-derived autologous DCs and Mphs loaded ex vivo with particular whole irradiated cancer cells which generates optimally activated immunostimulatory antigen-presenting cells (APCs) as a superior method for stimulating robust and long-lasting immunity to a particular cancer in vivo as compared with more traditional vaccination methods. Compositions, methods of use and methods for preparation of these DCs and Mphs with cancer cells are also disclosed herein.

Disclosed herein are methods and compositions related to identification, isolation, and targeting of first responder dendritic cells (FRs). Aspects of the disclosure are directed to FR-targeting agents and methods for use of such agents, including methods for directing a diagnostic, imaging, or therapeutic molecule (e.g., an antigen) to FRs. The present disclosure includes pharmaceutical compositions comprising an FR-targeting agent and an antigen or polynucleotide encoding an antigen. Also disclosed are methods for stimulating an immune response comprising targeting an antigen to FRs.

The present invention provides macrophages genetically modified to express IL-31 or both IL-31 and a chimeric antigen receptor (CAR) for treatment of cancer. It further provides methods for treatment of cancer comprising administration of IL-31 along with genetically unmodified macrophages or genetically modified to express a CAR.

Methods and compositions for treating cancers (e.g., neural cancers) by dendritic cell vaccination are provided herein.

Methods are disclosed for the generation of immunosuppressive regulatory T cells. The methods can include contacting a population of CD4+CD25? T cells with a T cell receptor (TCR)/CD3 activator, a TCR co-stimulator activator, and rapamycin. Kits for the generation of immunosuppressive regulatory T cells, methods of use, and cell populations are also disclosed.