The present invention relates to compositions and methods for producing an immune response or reaction, as well as to vaccines, kits, processes, cells and uses thereof. This invention more particularly relates to compositions and methods of using a synthetic viral particle to produce, modify or regulate an immune response in a subject. In a more preferred embodiment, the invention is based, generally, on compositions using synthetic viral particles as an adjuvant and/or vehicle to raise an immune response against selected antigen(s) or epitopes, in particular a cellular and/or a humoral immune response.

The present disclosure provides methods for generating Otub 1 deficient T cells and natural killer (NK) cells and compositions comprising engineered T cells expressing a reduced amount of Otub 1. Further provided are methods of treating cancer comprising administering the Otub 1 deficient T cells and/or NK cells to a subject in need thereof.

The present application provides methods of enhancing T cell function (e.g., expansion, persistence and/or effector functions), particularly by genetic modification of the Regnase-1, Batf, and additional genes (alone or in combination). The application also provides modified T cells manufactured using the methods provided by this invention and related pharmaceutical compositions. The application further provides methods of using the modified T cells for treating a disease (e.g., a cancer or an infectious disease).

The present invention provides a kit of vectors comprising a first and second viral vector, wherein the first viral vector comprises a transgene of interest (TOI), and presence of the second viral vector in a host cell is required for integration of the first viral vector TOI into the host cell genome.

A Thy1 gene promoter specifically expressed in neurons and a recombinant vector including the Thy1 gene promoter are provided. The Thy1 gene promoter may be utilized to regulate an expression of a target gene in preparation of an animal model similar to a human.

The present application relates to the field of immunotherapy, more particularly to the field of adoptive cell therapy (ACT). Here, multiple shRNAs, designed to downregulate multiple targets are proposed. Also proposed are polynucleotides, vectors encoding the shRNA and cells expressing such shRNAs, alone or in combination with a chimeric antigen receptor (CAR). These cells are particularly suitable for use in immunotherapy.

The disclosure provides vectors for treating cancers, method of producing such vectors and methods of use of the vectors.

The present application is directed to a method of treating osteoarthritis, which includes obtaining a member of a transforming growth factor superfamily of proteins; obtaining a population of cultured mammalian cells that may contain vector encoding a gene, or a population of cultured connective tissue cells that do not contain any vector encoding a gene; and then transferring the protein and the connective tissue cells into an arthritic joint space of a mammalian host, such that the activity of the combination within the joint space results in regenerating connective tissue.

The present disclosure provides chimeric antigen receptors (CARs), particularly CARs that have enhanced antitumor properties and/or can be regulated by safety switches. Also provided are polypeptides of the CARs and other related molecules, polynucleotides, vectors, and cell compositions comprising the same. Pharmaceutical compositions comprising the polypeptides, polynucleotides, vectors, or cells of the present disclosure, and their uses in treating a cancer in a subject are also provided.

Nucleic acid molecules comprising a nucleotide sequence encoding an activating chimeric antigen receptor (aCARs) are provided, said aCARs comprising (i) an extracellular binding-domain specifically binding an antigen selected from an antigen of the commensal gut microflora and a self-cell surface antigen specific to the lamina propria (LP) or submucosa of the gastrointestinal tract; (ii) a transmembrane domain; (iii) an intracellular domain including at least one signal transduction element that activates and/or co-stimulates a T cell; and optionally (iv) a stalk region linking the extracellular domain and the transmembrane domain. Compositions and vectors comprising the nucleic acid molecules encoding the aCAR as well as methods for preparing regulatory T cells comprising the vectors and expressing the aCARs are further provided as are methods for treating or preventing a disease, disorder or condition manifested in excessive activity of the immune system in a subject, comprising administering to said subject the mammalian Treg expressing on its surface an aCAR. The regulatory T cells optionally express a membrane-bound homodimeric IL-10 conferring a stable Tr1 phenotype.