Methods of expanding tumor infiltrating lymphocytes (TILs), including peripheral blood lymphocytes and marrow infiltrating lymphocytes, from blood and/or bone marrow of patients with hematological malignancies, such as liquid tumors, including lymphomas and leukemias, and uses of such expanded TILs in the treatment of diseases such as cancers and hematological malignancies are disclosed herein.

The present disclosure provides for methods to produce B cell-expanded Tregs that are more stable and more effective than donor-specific Tregs for suppressing polyclonally activated T cells. In certain embodiments, the present polyclonal Tregs can react to many donors, not just a specific donor.

Systems, compositions, and methods for the treatment of a liver disorder is disclosed. The systems, compositions, and methods include use of activated T regulatory cells for alleviating, treating, or reducing a liver disorder. The T regulatory cells may be allogeneic T regulatory cells that may be present in an amount of about 510.sup.5 to 210.sup.6 cells. The liver disorder needing treatment may be hepatitis, cirrhosis, chronic liver disease, acute liver disease, or liver failure.

Graft-versus-host disease (GVHD) is a lethal complication of allograft transplantation. The current strategy of using immunosuppressive agents to control GVHD may cause general immune suppression and limit the effectiveness of allograft transplantation. Adoptive transfer of regulatory T cells (Treg) can prevent GVHD in rodents, indicating the therapeutic potential of Treg for GVHD in humans. However, the clinical application of Treg-based therapy is hampered by the low frequency of human Treg and the lack of a reliable model to test their therapeutic effects in vivo. Human alloantigen-specific Treg are generated from antigenically-nave precursors in a large scale ex vivo using allogeneic activated B cells as stimulators. Here, a human allogeneic GVHD model is established in humanized mice to mimic GVHD after allograft transplantation in humans. The ex vivo-induced CD8.sup.hi Treg can control GVHD in an allo-specific manner by reduction of alloreactive T-cell proliferation, and inflammatory cytokine and chemokine secretion within target organs through a CTLA-4-dependent mechanism in humanized mice. Importantly, the Tregs can induce long-term tolerance effectively without compromising general immunity and graft-versus-tumor (GVT) activity.

Herein is reported a method for co-cultivating B-cells in the presence of phorbol myristate acetate, IL-1beta, TNFalpha, IL-2, IL-10 and IL-6.

Provided herein are methods for producing stimulated populations of regulatory B cells comprising treating an isolated population of B cells with stimulatory agents, such as CpG oligonucleotides, BCR ligation, and CD40 ligand. Also provided herein are methods of treating immune disorders, such as chronic graft versus host disease, with the stimulated population of regulatory B cells.

Methods and compositions for treating cancer are disclosed. The compositions comprise immune cells pretreated with ponatinib, or immune cells co-administered with ponatinib, where ponatinib promotes survival and anti-cancer cytotoxicity of the immune cells.

Embodiments of the present disclosure concern improvements to cell therapy for cancer. In certain embodiments, an immune cell lacks expression of hematopoietic growth factor receptor c-MPL (myeloproliferative leukemia), the receptor for thrombopoietin (TPO), and supplementation of this effect allows an improvement for cancer cell therapy, including of hematological malignancies. In specific embodiments, immune cells comprise recombinant c-MPL expression or parts thereof and the cells have enhanced co-stimulation and cytokine signals and improved activation, persistence, and anti-tumor function compared to cells that lack recombinant c-MPL expression.

The present disclosure provides, in part, a culture medium comprising: interleukin-2; lipopolysaccharide; one, two or more antibiotics; animal serum; and a growth factor, and methods for using same.

The present invention relates to a cancer-specific tumor antigen neoepitope represented by any one of SEQ ID NOs: 1 to 184, an antigen-presenting cell loaded with the neoepitope, and a method for activating T cells for cancer treatment using the antigen-presenting cell. An antigen-presenting cell, that is, a dendritic cell, loaded with a cancer-specific tumor antigen epitope provided in the present invention enables rapid and effective induction of differentiation and proliferation of cancer antigen-specific T cells, preferably memory T cells, and the memory T cells thus activated can treat a cancerous or neoplastic condition or prevent recurrence, progression, or metastasis of cancer while avoiding the defense mechanism of cancer cells.