The present disclosure is directed to a feeder-cell free methods of producing an expanded natural killer (NK) cell preparation. This method comprises providing a starting preparation of NK cells and treating the starting preparation with a natural killer cell p30-related protein (NKp30) modulating agent alone or with other expansion agents as described herein. The method further involves culturing the treated preparation under conditions effective to expand the starting preparation of NK cells to produce an expanded NK cell preparation. Other aspects of the disclosure related to therapeutic preparations of NK cells produced in accordance with the methods described herein.

The present invention relates to artificial antigen presenting cell (aAPC) scaffolds to provide cells with specific functional stimulation to obtain phenotypic and functional properties ideal to mediate tumor regression or viral clearance. In particular, the scaffolds of the present invention comprise stabilized MHC class I molecules comprising a heavy chain comprising an alpha-1 domain and an alpha-2 domain connected by a disulfide bridge, wherein said MHC class I molecules are free of antigenic peptide. The scaffolds can be loaded with antigenic peptide on demand, providing an agile platform for effective expansion and functional stimulation of specific T cells in a peptide-MHC-directed fashion.

The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

A feeder cell for culturing natural killer (NK) cells, genetically engineered to express membrane bound interleukin-18 (mbIL-18), membrane bound interleukin-21 (mbIL-21), and/or OX40L. A method of proliferating NK cells, including: obtaining a blood sample containing a population of NK cells; and contacting at least a part of the population of NK cells with a genetically engineered cell, where the genetically engineered cell is genetically engineered to express mbIL-18, mbIL-21, and/or OX40L.

A cell genetically engineered for activating natural killer (NK) cells. The genetically engineered cell for activating NK cells synergistically induces the proliferation and activation of NK cells in a sample, thereby producing effects that can be usefully utilized in a method of proliferating NK cells, a method of measuring NK cells proliferated by the method, or an activation degree of NK cells, or a method of diagnosing an NK cell activity-related disease. A feeder cell for culturing a natural killer (NK) cell, genetically engineered to express membrane bound interleukin-18 (mbIL-18) and membrane bound interleukin-21 (mbIL-21).

Provided herein are methods for ex vivo expansion of a specialized subset of natural killer (NK) cells, and compositions containing such NK cells. Also provided are methods for identifying or detecting a specialized subset of NK cells. Also provided are methods for treating diseases and conditions such as cancer using provided compositions, including in combination with an antibody capable of binding to disease-associated tissues or cells, such as tumor cells or infected cells.

Disclosed herein are expanded NK cells and methods of using thereof for treating, preventing, reducing, and/or inhibiting a microbial infection.

The disclosure provides methods of treating coronavirus infections (e.g., COVID-19) by administering hematopoietic stem cells, with or without an immune checkpoint inhibitor (e.g., PD-1 antagonist). The disclosure also provides methods of treating coronavirus infections (e.g., COVID-19) by adoptive cell transfer of polyclonal T cells and coronavirus-specific T cells (e.g., SARS-CoV-2-specific T cells).

A method of treating a metastatic lesion that presents a peptide containing SLLQHLIGL (SEQ ID NO: 310) on a cell surface, including selecting a patient having a metastatic lesion and administering to the patient a composition containing recombinant T lymphocytes or activated T lymphocytes that express a T cell receptor, or a functional fragment thereof, that is reactive with, or binds to, an MHC ligand containing SLLQHLIGL (SEQ ID NO: 310).

This disclosure provides methods of making immune effector cells (for example, T cells, NK cells) that comprise (i) a nucleic acid molecule that encodes a controllable chimeric antigen receptor (CCAR) or (ii) a nucleic acid molecule that encodes a CAR and a regulatory molecule, and compositions generated by such methods.