The present invention relates to compositions, methods, and kits for eliciting an immune response to at least one CMV antigen expressed by a cancer cell, in particular for treating and preventing cancer. CMV determination methods, compositions, and kits also are provided.

The invention provides an isolated, purified population of human cells comprising CD8.sup.+ T cells with reduced Cbl-b activity. The invention provides uses of such cells in methods for inducing or enhancing an anti-tumor immune response in a subject. These methods comprise: (a) providing a cell population, from a subject or from another source, which comprises CD8.sup.+ T cells, (b) reducing Cbl-b activity in the CD8.sup.+ T-cells, (c) administering the cells of step (b) to the subject. The invention provides methods for making CD8.sup.+ T cells that do not require stimulation through a co-receptor in order for the cell to become activated or proliferated in response to contact via its T cell receptor. Such methods are based upon reducing function of Cbl-b. The invention also provides methods for identifying agents which affect Cbl-b expression or activity.

The HIV-specific cytotoxic T lymphocyte (CTL) response is a critical component in controlling HIV replication and is an important part of the ultimate failure to eradicate the virus. Disclosed herein are methods for genetically enhancing the HIV-specific CTL response to allow long-term viral suppression or viral clearance. Human hematopoietic stem cells (HSCs) were genetically modified such that they differentiate into mature CTLs that will kill HIV infected cells. As disclosed herein, the functional effector cells are not human leukocyte antigen (HLA)-restricted. As disclosed herein, stem cells are transduced with non-HLA restricted chimeric antigen receptors (CARs) that allow the recognition of HIV or HIV-infected cells when expressed by a CTL. These CARs are hybrid molecules that contain an extracellular HIV recognition domain and an intracellular TCR-zeta signaling domain. The CTL response may be enhanced through the targeting of T cell inhibitory receptors. The methods and compositions disclosed herein may be used to engineer antiviral immunity and HIV-specific CTL responses in vivo. Also disclosed herein are methods and compositions for the treatment of chronic viral infections such as HIV.

The present invention provides a time and space adjustable system for inhibiting pathological target cells. The system comprises: (1) fusion protein, comprising polypeptide tags and binding molecules for specifically recognizing pathological target cells; and (2) chimeric antigen receptor immune effector cells, which express binding molecules for specifically recognizing the polypeptide tags. Disclosed is a technical solution based on a tumor-specific chimeric antigen receptor (CAR) technology, in which the immune effector cells can target pathological target cells only in the presence of a mediator, and the CAR immune effector cells can expand continuously and have killing effect on tumor cells; the CAR immune effector cells have no effect in the absence of a mediator.

There is provided herein a method for expanding human CD4?CD8? regulatory T cells (DN Tregs) from a population of cells comprising DN Tregs, comprising: culturing the population of cells with artificial antigen presenting cells (APCs), prefer-ably the DN Tregs are ??-TCR?CD56? or alternatively ??-TCR+.

Cell preparations comprising a pooled and enriched, mononuclear apoptotic cell population, and a method of preparing this cell preparation are described. The pooled mononuclear apoptotic cell preparation may be obtained from pooled, allogeneic white blood cell fractions that are pooled prior to or following induction of apoptosis. Further, described herein are methods of use of these pooled apoptotic cell preparations for treating an immune disease, an inflammatory disease, an autoimmune disease, or infertility in a subject. For example, a pooled apoptotic cell preparation may be used to treat graft versus host disease (GVHD) in an allogeneic subject.

The present invention concerns methods and compositions related to T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies. In aspects of the invention, T cells that are CD70-specific are employed. In particular aspects, there are T cells expressing a novel molecule that comprises the full-length CD70 receptor (CD27) fused to the zeta signaling domain of the T-cell receptor complex. Such T cells recognized CD70-positive tumor cells and have cytolytic activity against CD70-positive cancer cells.

Embodiments of the disclosure include methods and compositions related to immunotherapy that targets CD5. In particular embodiments, immune cells engineered to comprise a chimeric antigen receptor (CAR) that targets CD5 are contemplated, and uses thereof. In particular embodiments, the immune cells expressing the CAR do not commit fratricide to any great extent against T cells that express CD5 and which are endogenous to an individual receiving the immune cells.

The inventors demonstrate that treatment of young, suckling mice with a glycolipid derived from Helicobacter pylori activates NKT cells in a CD1d-restricted fashion, and is protective against AHR in a model of allergen-induced asthma. The inventors further found that this protective effect can be transferred by NKT cells exposed to the glycolipid, and is associated with the expansion of a suppressive double-negative NKT cells and Foxp3.sup.+ T.sub.Reg cells. The inventors also demonstrate herein that pretreatment of adult mice with a glycolipid derived from Helicobacter pylori partially suppresses airway hyperreactivity and inhibits BAL inflammation in an ozone-exposure model. Accordingly, provided herein are compositions and methods for the treatment and prevention of inflammatory diseases, such as asthma or autoimmune diseases, in a subject in need thereof.

A method for the expansion of tumor-specific T-cells includes obtaining an enriched population of T-cells from a subject with cancer; and contacting the enriched population of T-cells ex-vivo with: (i) an anti-CD3 antibody, an anti-CD28 antibody, and/or functional fragments thereof, and (ii) a VEGF inhibitor, to activate and expand the T-cells.