The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

Embodiments of the instant disclosure relate to novel compositions, methods and systems for generating ILC cells. In certain embodiments, the present disclosure provides for a composition including a hematopoietic progenitor cell expressing CD48 and at least one of a CD48 ligand, a CD48 agonist or a CD48 antagonist in order to induce production of ILC2 or ILC3 (for example, NCR.sup.+ ILC3 and LTi-ILC3) cell populations. In other certain embodiments, the present disclosure provides methods of treating one or more health condition or immune-mediated condition in a subject by administering an effective amount of a composition of ILC2 or ILC3 cells generated using methods disclosed herein.

Described are protocols, compositions of matter and therapeutic means useful for treatment of ovarian failure caused by oncology treatments. The utilization of natural killer cells allows for dual activity of tissue regeneration in the ovary, while concurrently inhibiting possibility of oncology relapse. In embodiments NK cells are injected as an adjuvant to stem cell and/or regenerative cell therapy to not only enhance therapeutic effect but also to reduce probability of tumor relapse.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

The present invention relates to a method for inducing amplification of human type I NKT cells in vitro using a “specific stimulant+staged cytokine” mode, which consists of two culture stages, wherein the first culture stage focuses on specific amplification of the number of the type I NKT cells, in which a specific stimulant α-GalCer is used to advantageously amplify the type I NKT cells and α-GalCer-loaded CD1d-expressing cells are used to stimulate continuous proliferation of the type I NKT cells while adding cytokines IL-2 and IL-7 to assist growth of the type I NKT cells; and the second culture stage is to synchronously perform amplification of the number of the type I NKT cells and guide directed function differentiation, in which CD1d-expressing cells incubated with α-GalCer continue to stimulate proliferation of the type I NKT cells while adding IL-2, IL-7 and IL-15 to assist amplification of the type I NKT cells and guide differentiation, and IL-12 is added to the culture system 1-2 days before the end of culture to guide further directed differentiation of the type I NKT cells and enhance their killing activity. The method of the present invention is simple to operate, can greatly amplify the type I NKT cells in vitro while improving the killing activity of the amplification products, and is suitable for large-scale production.

Compositions and methods for NK cell based treatments, and particularly NK cells that express and intracellularly retain IL-2, are presented in which the NK cells are stimulated with a chimeric protein that has a cancer cell targeting portion and an IL-12 portion. Beneficially, such chimeric protein has substantially reduced systemic toxicity and induces IFN-γ secretion in a targeted manner. Moreover, chimeric proteins contemplated herein also significantly enhanced IFN-γ secretion in NK cells that express and intracellularly retain IL-2 as compared to native NK cells. Preferred chimeric proteins comprise SEQ ID NO:1 or SEQ ID NO:2, and SEQ ID NO:3.

Provided are methods of producing an isolated population of cells for adoptive cell therapy comprising use of at least one cell permeable Ca.sup.2+ dye. Further embodiments of the invention provide isolated populations of cells produced by the methods, related pharmaceutical compositions, and related methods of treating or preventing cancer in a patient.

The present invention refers to a method for the production of activated CD3-CD56+ NK cells, activated CD3-CD56 NK+ cells obtainable with the method, their use, in particular for the treatment of a tumor, preferably a hepatocellular carcinoma (HCC), for use in the treatment and/or prevention of an HCV infection, for use in the treatment and/or prevention of a post-liver transplant HCV reinfection, or for use for prevention of a post-liver transplant HCC recurrence. The invention also concerns pharmaceutical compositions including the activated CD3-CD56+ NK cells.

Provided herein are methods of treating cancer in a subject including detecting an amount of PD-L1(+) natural killer (NK) cells in a biological sample from the subject and treating the subject with an anti cancer therapy. Provided herein are methods of treating cancer in a patient including isolating natural killer (NK) cells from a subject, producing a population of PD-L1(+) NK cell from the isolated NK cells, and administering the population of PD-L1(+) NK cells into the patient.