The present invention relates to a method of using a receptor (e.g., chimeric antigen receptor—CAR) that activates an immune response upon binding a cancer cell ligand in conjunction with a target-binding molecule that targets a protein or molecule for removal or neutralization to generate enhanced anti-cancer immune cells. The present invention also relates to engineered immune cells having enhanced therapeutic efficacy and uses thereof.

Provided herein are genetically modified (GM) natural killer (NK) cells and methods of producing populations of GM NK cells. Further provided herein are methods of using the GM NK cells described herein, to, e.g., suppress the proliferation of tumor cells, or to inhibit pathogen infection, e.g., viral infection. In certain alternatives, GM NK cells provided herein lack expression of CBLB, NKG2A and/or TGFBR2 and/or function or show reduced expression and/or function of CBLB, NKG2A and/or TGFBR2. In certain alternatives, GM NK cells provided herein comprise modified CD16.

Provided herein are methods and customized media compositions for culturing CIK NKT cells.

The present invention relates to a culture method for increasing the content of NK cells. According to the present invention, the growth rate of immune cells including NK cells can be increased not only in cancer patients but also in persons who are genetically susceptible to cancer or elderly people, and an NK cell fraction and cell-killing ability can also be enhanced.

The invention provides Natural Killer (NK) cells that have a reduced or ablated Signal Regulatory Protein Alpha (SIRPα-) function when compared to a NK cell having an unmodified SIRPα-function that effectively kills a population of cancer cells that express CD47.

Natural Killer (NK) cells represent a potent therapeutic for patients suffering from cancer or infectious diseases. NK cells typically represent a minor fraction of the lymphocytes and express multiple receptors that interact with human leukocyte antigen (HLA). Disclosed are methods of expanding NK cells and compositions of NK cells for administration in patients. The methods described herein can be used to identify donor NK cells for administration to a recipient subject. The NK cell compositions disclosed herein can be used to treat a number of diseases including cancer and infectious diseases.

Modified natural killer (NK) or T cells expressing hematopoietic growth factor receptors are provided. In some embodiments, the NK cells or T cells express a thrombopoietin receptor or an erythropoietin receptor. Methods of treating a subject with cancer are also provided, including administering the modified NK cells or T cells to the subject in combination with a thrombopoietin receptor agonist or erythropoietin receptor agonist, and in some example, interleukin-2, particularly reduced or low-dose amounts of IL-2.

Methods of infection, hold times and storage temperatures are provided to extend the viability and stabilize the phenotype of the cytolytic cells as a monotherapy and cytolytic cells containing an oncolytic virus capable of cell cycle arrest. Pre-infection of effector cells prior to storage at 4° C. or room temperature resulted in sustained viability of expanded immune cells and a higher percentage of CD3+/CD56+ T cells including a higher percentage of those CD3+/CD56+ T cells expressing the NKG2D receptor. In some embodiments, viral infection of immune cells increases the expression of the NKG2C, D and E receptors and influence the migration, binding and cytolytic activity towards tumor cells representing synergy between the immune cell and oncolytic virus in attacking and lysing tumor cells.

Compositions disclosed herein, and methods of use thereof included those for treating or preventing SARS-CoV-2 vims infection in a subject in need, including methods of extending of the survival of a subject suffering from COVID-19, and reduction of organ dysfunction or failure due to COVID-19 or associated symptoms. Methods of treating or preventing COVID-19 in a subject in need includes administering compositions comprising early apoptotic cells or early apoptotic cell supernatants. Compositions and methods of use thereof may reduce the negative proinflammatory effect accompanying COVID-19 and symptoms thereof. Further, anti-inflammatory cytokine release may be increased. In certain instances, compositions may include additional agents.

The disclosure features methods and compositions for differentiating stem cells into hematopoietic stem and progenitor cells (HSPC) and/or Natural Killer (NK) cells. The methods and compositions described herein are used to differentiate stem or progenitor cells having at least one gene-edit that is maintained in the differentiated cell. Also provided are differentiated cells produced using the methods and compositions described herein for therapeutic applications.