Technology provided herein relates to methods of treating cancer comprising administering to a subject in need thereof a first stem cell (SC) modified to release an oncolytic virus and a second SC which is gene edited to inactivate a receptor for the oncolytic virus, thereby generating a stem cell resistant to the virus, wherein the second SC is also engineered to express an immunomodulatory polypeptide agent. Compositions comprising a first and second SC, and uses thereof, are also provided herein.

Methods and compositions are provided to augment the conversion of mixed hematopoietic cell chimerism to complete donor cell chimerism following allogeneic hematopoietic cell transplantation (HCT), where such transplantation may be utilized for treatment of cancer such as leukemia and lymphoma or for other conditions requiring reconstitution of the hematopoietic system, e.g. treatment of anemias, thalassemias, autoimmune conditions, and the like. The present invention improves on conventional DLI by utilizing a composition of substantially purified donor memory CD8.sup.+ T cells as DLI following allogeneic HCT, where the cells are administered at a suitable time following transplantation. The methods provide for a more complete donor chimerism, and have the further benefit of killing tumor cells without GVHD. The memory CD8+ T cells may include one or both of central and effector memory T cells, usually both.

Disclosed herein are genome editing systems and related methods which allow for treatment of Hyper IgM Syndrome, a group of disorders characterized by defective CD40 signaling. The compositions and methods described herein rely on the use of donor templates comprising a CD40L exons to restore proper CD40 signaling and B cell class switch recombination.

Disclosed are methods of preparing thymic emigrant cells in vitro, isolated or purified thymic emigrant cells prepared by the methods, and pharmaceutical compositions comprising the same. Further disclosed are methods of treating or preventing a condition in a mammal comprising administering the thymic emigrant cells or pharmaceutical compositions comprising the same to the mammal.

Provided is a method for preparing and using cell ghosts with active factors as a synergist of a lymphocyte in vitro culture. The method for preparing cell ghosts comprises: washing a cell to obtain a washed cell; and cleaving the washed cell to obtain cell ghosts, wherein the cell has cytokines capable of promoting the proliferation and differentiation of lymphocytes on their surface.

Inhibition of the VIP signaling pathway with VIP antagonist is contemplated. In certain embodiments, the disclosure relates to methods of enhancing the immune response to a cell therapy comprising administering a VIP antagonist to a subject in combination with a cell. In certain embodiments, the subject is diagnosed with leukemia or lymphoma. In certain embodiments, the cell is a blood cell, bone marrow cell, leukocyte, T-cell, natural killer cell, a hematopoietic stem cell, a G-CSF mobilized or non-mobilized blood mononuclear cell.

Disclosed are compositions and methods of treating muscular dystrophies, including Duchenne Muscular Dystrophy (DMD) through administration of fibroblasts and modified fibroblasts systemically and locally. In certain embodiments, fibroblast cells are utilized for replacement of dystrophin through fusion and/or other means of horizontal gene transfer. In other embodiments, the disclosure teaches the use of fibroblasts for reduction of inflammatory reactions and/or immunological reactions which propagate and enhance myodestructive aspects of Duchenne Muscular Dystrophy. In other embodiments, fibroblasts are utilized as vectors for gene therapy and/or gene modifications approaches.

The invention is directed to methods and compositions for cell-based targeted delivery of predetermined compounds to a population of target cells. In some embodiments, methods of the invention include providing cytotoxic lymphocytes genetically modified to produce and sequester in lytic granules fusion proteins comprising a granzyme, or other effector agent, and a predetermined protein, so that upon specific contact of the cytotoxic lymphocytes with the target cells, the granzyme-perforin pathway of the cytotoxic lymphocytes is activated, leading to the delivery of the fusion protein to the cytosols of the target cells.

This disclosure relates to a cellular-based therapies for modulating the level of regulatory T cells (Treg) and/or the level of pro-inflammatory T cells (Th17/Th1). To provide these therapeutic effects, a combination comprising at least one a cellular pro-tolerogenic preparation and at least one a cellular pro-inflammatory preparation are administered sequentially.

Provided are transplants and methods for augmenting formation and restoration of organ and tissue, for example, bone formation, by administering autologous or allogeneic human embryonic-like adult stem cells (ELA cells). Also provided is a method for augmenting formation of tissues and organs by administering a transplant having ELA stem cells or combination of ELA stem cells.