Immunotherapeutic methods and compositions are contemplated where one or more neoepitopes and/or tumor associated antigens are produced in, or delivered to dendritic cells, and in which so modified dendritic cells are co-cultured with immune competent cells of a patient, preferably in the presence of stimulatory signals. Cells are then transfused to the patient that has preferably undergone immune checkpoint inhibition treatment.

Described herein are agents and methods for targeting antigen-specific B cells using engineered T cells, such as regulatory T cells or cytotoxic T cells, or bi-specific antibodies. The agents and methods can be used to reduce undesirable immune responses.

The present invention relates to a population of lymphocytes comprising at least 90% CD3+ T cells and less than 5% B cells, wherein at least 70% of said T cell portion are viable, at least 20% are CD27/CD28 double positive and less than 10% are triple positive for CD45RA, CD57 and KLRG1 and a method for expansion of a population of lymphocytes specific for one or more antigens comprising a single culture phase.

The present invention relates to a method for producing antigen-specific T cells and their use in a method for the treatment or prevention of cancer.

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-na?ve 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.

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-na?ve 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.

Embodiments of the disclosure concern methods and compositions for immunotherapy for human papillomavirus infection and diseases associated therewith. In specific embodiments, methods concern production of immune cells that target one or more antigens of HPV16 and/or HPV18, including methods with stimulation steps that employ IL-7 and IL-15, but not IL-6 and/or IL-12. Other specific embodiments utilize stimulations in the presence of certain cells, such as costimulatory cells and certain antigen presenting cells.

The present invention provides a method for in-vitro culturing and expanding natural killer (NK) cells in a cell culture medium comprising a population of NK cells, the method comprising a) adding an effective concentration of interleukin-21 (IL-21) at the beginning of the culturing process to said medium, b) adding repeatedly an effective concentration of interleukin-2 (IL-2) and/or interleukin-15 (IL-15) to said medium, and c) adding repeatedly feeder cells or membrane particles thereof to said medium, wherein said feeder cells are B cell derived which are EBV immortalized; and wherein said expansion of NK cells in said cell culture medium is maintained for at least 3 weeks.

A method of treating a cancer in a subject is disclosed, comprising: (1) isolating T cells from a subject; generating or expanding a population of T cells specific for a virus by a method comprising: stimulating T cells by culture in the presence of antigen presenting cells (APCs) presenting a peptide of the virus, wherein 10 to 25% of the media in which the cells are cultured is conditioned media obtained from a stimulation culture comprising T cells and APCs presenting a peptide of the virus; and (3) administering the generated or expanded population of T cells to a subject. Also disclosed are methods for generating or expanding a population of T cells specific for a virus.

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.