The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells. In some embodiments, the methods include reaction mixtures, and resulting cell formulations, that are created using whole blood, or a component thereof that is not a PBMC, and additionally comprise T cells and recombinant retroviral particles having polynucleotides that encode a CAR. In some embodiments, modified lymphocytes are reintroduced into a subject subcutaneously. In some embodiments, polynucleotides that provide T cells the ability to regulate cell survival and proliferation in response to binding to a CAR, are provided.

The present disclosure provides transposon-based systems for introducing cellular therapeutic products, such as CAR and TCR, into a target immune cell. The transposon-based systems can carry larger payloads than conventional viral vector-based technologies, simplifying multi-genetic editing and can reduce undesired recombination between homologous sequences in the payload. Also provided is a shortened autologous process that can be completed within a few days, within one day or even within a few hours. Even without immune cell activation, enrichment or expansion, the resulting cell populations achieve greatly higher in vivo therapeutic efficacy than the much lengthier autologous process that employs viral vectors.

The present disclosure provides compositions and methods for making and using engineered killer phagocytic cells for immunotherapy in cancer or infection by expressing a chimeric antigen receptor having an enhanced phagocytic activity, the chimeric receptor is encoded by a recombinant nucleic acid.

The present disclosure provides compositions of genetically modified cells that are hypoimmunogenic. The present disclosure also provides methods of making hypoimmunogenic cells and using hypoimmunogenic cells for the treatment of cancer and autoimmune conditions.

The present invention relates to a medicament for use in a method of preventing or treating cancer in a patient, wherein the medicament comprises at least two of the following populations of cells (i) to (iv): (i) a population of lymphokine-activated killer cells (LAKs), (ii) a population of cytokine-induced killer cells (CIKs), (iii) a population of ??-T-cells, (iv) a population of tumor-specific T-cells (CTLs), wherein the population of cells in (i) to (iv) are derived from autologous cells from said patient or from allogeneic cells from a donor, and pharmaceutical composition, kit or kit-of-parts related thereto.

Human or humanized tissues and organs suitable for transplant are disclosed herein. Gene editing of a host animal provides a niche for complementation of the missing genetic information by donor stem cells. Editing of a host genome to knock out or disrupt genes responsible for the growth and/or differentiation of a target organ and injecting that animal at an embryo stage with donor stem cells to complement the missing genetic information for the growth and development of the organ. The result is a chimeric animal in which the complemented tissue (human/humanized organ) matches the genotype and phenotype of the donor. Such organs may be made in a single generation and the stem cell may be taken or generated from the patient's own body. As disclosed herein, it is possible to do so by simultaneously editing multiple genes in a cell or embryo creating a niche for the complemented tissue. Multiple genes can be targeted for editing using targeted nucleases and homology directed repair (HDR) templates in vertebrate cells or embryos.

The present disclosure relates to a method for preparing a cancer-specific T cell based on peripheral blood or a peripheral immune organ for preventing or treating cancer, specifically including steps of: first, isolating an immune cell from peripheral blood or the peripheral immune organ; then, co-incubating with a nanoparticle and/or a microparticle loaded with a tumor whole-cell antigen for a period of time to activate the cancer-specific T cell; then, isolating a cancer-specific T cell activated by the tumor antigen; and, reinfusing the cancer-specific T cell into the body to exert an anti-cancer effect after in vitro expansion. According to the nanoparticle or microparticle prepared by the present disclosure, a tumor antigen component is loaded onto the microparticle and/or the nanoparticle to activate the cancer-specific T cell, and then the cancer-specific T cell is expanded and reinfused into a patient for treating cancer or preventing recurrence or metastasis. The cancer-specific T cell isolated by a sorting method has high specificity, and may prevent or treat cancer by killing cancer cells after expansion.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors or additional cells in combination therapies.