The present invention discloses methods, compositions and devices for improving tissue regeneration by suppressing the effects of several proinflammatory cytokines such as TNF-? and IFN-?. Compositions and devices of this invention will generally include one or more anti-inflammatory agent(s) capable of reducing the level of TNF-?, IFN-?, or both. Methods for improving tissue regeneration in accordance with this invention will generally have the step of applying a composition or device of the invention to a site in need of the composition or device. Also disclosed are methods for forming composition and devices of the invention and pharmaceutical compositions comprising one or more anti-inflammatory agent(s) effective of inhibiting or reducing the levels of TNF-?, IFN-?, or both.

Disclosed herein are conditioning regimens and methods for inducing MHC- or HLA-mismatched mixed chimerism by conditioning a recipient with radiation-free, low-doses of cyclophosphamide (CY), pentostatin (PT), and anti-thymocyte globulin (ATG) prior to transplantation of donor bone marrow cells. In certain embodiments, the donor bone marrow cells may be CD4+ T-depleted bone marrow cells. The conditioning regimens and methods may also include administering one or more populations of conditioning donor cells selected from donor CD4.sup.+ T-depleted spleen cells, donor CD8.sup.+ T cells, and donor G-CSF-mobilized peripheral blood mononuclear cells. The conditioning regimen is clinically acceptable and can be used for treating hereditary hematological diseases and autoimmune diseases, as well as for promoting organ transplantation immune tolerance.

The present invention provides compositions and methods for inducing a CAR mediated trans-signal in a T cell. The trans-signaling CAR T cells comprise a first CAR having a first signaling module and a second CAR having a distinct second signaling module. The present invention also provides cells comprising a plurality of types of CARs, wherein the plurality of types of CARs participate in trans-signaling to induce T cell activation.

DNA methylation profiles predictive of head and neck squamous cell carcinoma (HNSCC) patient prognosis, as well as therapeutic protein and adoptive cell compositions useful in the treatment of HNSCC.

Disclosed herein are methods of increasing numbers of monocytes to a tumor or cancer metastasis site in a subject. Non-limiting embodiments include administering or using a Nur77 polypeptide or subsequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14+ CD16.sup.+ monocytes and/or CD14dimCD16.sup.+(CD115.sup.+CD11b.sub.+GR1.sup.?(Ly6C?)) monocytes; CD14.sup.+CD16.sup.+ monocytes and/or CD14dimCD16.sup.+(CD115.sup.+CD11b.sup.+GR1.sup.?(Ly6C?)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist. Also disclosed herein are methods of increasing, stimulating, activating or promoting monocyte migration to or mobilization against a tumor or cancer metastasis in a subject. Non-limiting embodiments include administering a Nur77 polypeptide or sub-sequence thereof; a Nur77 agonist; a CX3CR1 agonist; CD14+ CD16+ monocytes and/or CD14dimCD16.sup.+(CD115.sup.+CD11b.sup.+GR1.sup.? (Ly6C?)) monocytes; or CD14.sup.+CD16.sup.+ monocytes and/or CD14dimCD16.sup.+(CD115.sup.+CD11b.sup.+GR1.sup.?(Ly6C?)) monocytes contacted with a Nur77 agonist or contacted with a CX3CR1 agonist.

Some embodiments of the present disclosure are directed to methods that include delivering to a subject a papillomavirus particle or soluble papillomavirus protein that targets a tumor, and delivering to the subject an immune cell expressing a receptor that binds to a surface antigen of the papillomavirus particle or soluble papillomavirus protein, respectively.

Disclosed herein are methods and compositions for inactivating CCR-5 genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs, such as adenovirus (Ad) vectors, and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also 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 present invention pertains to immunology, biomedicine field, specifically relates to a method for prevention or treatment of one or more of diseases relevant to the protein in the protein-cell conjugate, malignant tumors, infectious diseases caused by pathogenic microorganisms and autoimmune diseases. The method includes a step of administering to a subject in such need a prophylactically or therapeutically effective amount of a protein-cell conjugate, the said protein-cell conjugate is a conjugate formed by covalently linking a protein and a cell to a linker, respectively; the cell has free sulfhydryl groups distributed on its surface, when the cell is not linked to the linker; the linker is derived from a bifunctional cross-linking agent, and the bifunctional cross-linking agent comprises both a group capable of reacting with an amino group and a group capable of reacting with a sulfhydryl group.

Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.