The described invention provides a pharmaceutical composition comprising a therapeutic amount of an educated mononuclear cell product, a process for preparing the educated mononuclear cell product, and a method for treating a disease characterized by lymphocyte autoreactivity. Mononuclear cells from a diseased subject are co-cultured with a viable population of adherent umbilical cord blood stem cells at at least 80% confluence to form an educated mononuclear cell product. A therapeutic amount of the educated mononuclear cell product is returned by infusion intravascularly to the subject. The therapeutic amount is effective to modulate autoreactivity in a T cell compartment of the subject and to reduce symptoms of the disease characterized by lymphocyte autoreactivity.

The present disclosure relates generally to the manufacture of regulatory T cells (Tregs) for use in immunotherapy. In particular, the present disclosure relates to robust approaches for the expansion of alloantigen-reactive Tregs ex vivo. Alloantigen-reactive Tregs produced in this way are suitable for the induction and/or maintenance of immunologic tolerance in recipients of allogeneic transplants.

Disclosed in the present application are: a method for preparing in vitro/ex vivo antigen-specific cytotoxic T-cells by using B cells treated with biological response modifier; and a use thereof. The cytotoxic T-cells prepared by the method of the present application can be used advantageously for treating infectious disease and cancer and the like.

Production and use of novel therapeutic cells, called T-Vehicles, in the allogeneic Adoptive Cell Therapy setting allows a wide range of therapeutic benefits to accrue with minimal or no risk of GVHD. T-Vehicles are created from donor T cells that are altered to contain therapeutic attributes that do not include their native antigen receptors and can deliver therapeutic benefits irrelevant of their native antigen specificity. T-Vehicles can possess highly restricted native antigen specificity that renders them unable to recognize antigens present on normal cells and incapable of initiating GVHD, making them ideal transport vehicles to deliver various therapeutic attributes in vivo. In essence, production and use of T-Vehicles is a paradigm shift that opens the door to therapeutic application of T cells in ways not previously contemplated, independent of whether or not there is an HLA match between the donor and the recipient.

Regulatory B cells (tBreg) are disclosed herein. These regulatory B cells express CD25 (CD25.sup.+) a pan B cell marker such as B220 (B220.sup.+), and also express CD19 (CD19.sup.+). These regulatory B cells suppress resting and activated T cells in cell contact-dependent manner. Methods for generating these regulatory B cells are also disclosed herein, as are methods for using these regulatory B cells to produce regulatory T cells (Treg). In some embodiments, methods for treating an immune-mediated disorder, such as an autoimmune disease, transplant rejection, graft-versus-host disease or inflammation, are disclosed. These methods include increasing regulatory B cell number or activity and/or by administering autologous regulatory B cells. Methods for treating cancer are also disclosed herein. These methods include decreasing regulatory B cell activity and/or number.

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 relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interaction with the immune system.

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.

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 a population of immune cells, such as natural killer cells or CAR-modified natural killer cells, using exosomes, and methods of producing the exosomes from a population of 721.221 cells transduced or transfected with a membrane-bound IL-21 (mIL-21) or a population of 721.22 cells transduced or transfected with a mIL-21 and B7-H6. Methods of treating a cancer or an infectious or immune disease, wherein immune cells expanded using the exosomes are administered to a subject with the cancer or the infectious or immune disease are also provided.