A 3D decellularized bone scaffold seeded with cancer cells, such as prostate cancer cells or Ewing's sarcoma is provided. The three-dimensional includes Ewing's sarcoma (ES) tumor cells; and an engineered human bone scaffold. The engineered human bone scaffold further includes osteoblasts that secrete substance of the human bone, and osteoclasts that absorb bone tissue during growth and healing. The engineered human bone scaffold includes the tissue engineered three-dimensional model which recapitulates the osteolytic process. The engineered human bone scaffold is engineered by co-culturing of osteoblasts and osteoclasts. The osteoblast is produced by cell differentiation process from mesenchymal stem cells. The osteoclast is produced by cell differentiation from human monocytes, wherein the human monocytes are isolated from buffy coats. The scaffold can be used with cancer cell lines to identify therapeutic targets to slow, stop, and reverse tumor growth and progression as well as to predict the efficacy of potential therapeutics.

Provided herein are methods for enhancing gene therapy in an individual by administering an IRAK degrader with the gene therapy to suppress innate immunity to the gene therapy. In some embodiments, the gene therapy uses an adeno-associated virus (AAV) vector, an adenovirus vector, a lentivirus vector, a Herpes simplex virus (HSV) vector or a lipid nanoparticle. Also provided herein are methods for selecting an individual for treatment with an IRAK degrader in combination with a gene therapy agent.

Methods are provided for treating blood monocytes to produce functional antigen presenting dendritic cells. An extracorporeal quantity of a subject's blood is treated to separate the blood and produce a leukocyte concentrate comprising monocytes and plasma containing proteins. The leukocyte concentrate comprising monocytes and plasma containing proteins is pumped through a plastic treatment device, such as a photopheresis device. The resulting treated cells may be incubated for a sufficient period of time to allow the monocytes to form dendritic cells, or the treated cells may be reinfused directly to the subject.

Disclosed are methods of obtaining a cell population enriched for T cells having antigenic specificity for a cancer-specific mutation using in vitro stimulation of memory T cells. Also disclosed are related methods of isolating a T cell receptor (TCR), populations of cells, TCRs or antigen-binding portions thereof, pharmaceutical compositions, and methods of treating or preventing cancer.

The disclosure relates to a method of reprogramming one or more somatic cells, e.g., partially differentiated or fully/terminally differentiated somatic cells, to a less differentiated state, e.g., a pluripotent or multipotent state. In further embodiments the invention also relates to reprogrammed somatic cells produced by methods of the invention, to chimeric animals comprising reprogrammed somatic cells of the invention, to uses of said cells, and to methods for identifying agents useful for reprogramming somatic cells.

The invention relates to progenitor cells of mesodermal lineage and their use in therapy.

A method for producing natural killer cells is disclosed. The method comprises isolating peripheral blood mononuclear cells (PBMCs) from a blood sample; isolating at least one of CD56+ cells and/or CD3/CD56+ cells from the PBMCs; and co-culturing the at least one of CD56+ cells and/or CD3/CD56+ cells with a combination of feeder cells in the presence of a cytokine. A composition for treating cancer is also disclosed. The composition comprises the CD56+ natural killer cells produced by the disclosed method and a cytokine.

Vectors and methods are disclosed for immortalizing mammalian cells by co-expression of v-raf and v-myc proteins. A replication-defective viral vector is used for improved safety. The vector comprises an optional marker gene, and is especially useful for producing an immortalized macrophage by a method that involves contacting the vector with a monocyte, proliferatively growing the monocyte, growing the monocytic cell on a solid surface, and then growing the monocytic cell on a porous surface. An immortalized macrophage is also disclosed.

Modified lymphocytes that ectopically express an endogenous gene of interest, such as a gene encoding a chemokine cell surface receptor, are described. Also described are methods of producing the lymphocytes by delivery of transcriptional activator complexes, as well as methods of targeting cells with cognate chemokines, in order to treat various disorders.

An object of the present invention is to provide an effective method for producing a population of NK cells for cell therapy. Another object of the present invention is to improve in vitro amplification efficiency of NK cells. A still another object of the present invention is to flexibly increase signals required for licensing of NK cells. There is provided a method for producing a cell population including NK cells, which comprises preparing a cell population of mononuclear cells originating in a plurality of donors and including NK cells, and incubating the prepared population of mononuclear cells under conditions effective for treating and proliferating NK cells to proliferate NK cells.