There is provided method for making a cell composition which comprises step of transducing a population of cells with a mixture of at least two viral vectors, wherein at least one vector comprises a nucleic acid sequence which encodes a chimeric antigen receptor (CAR); and wherein at least one vector comprises a nucleic acid encoding an activity modulator which modulates the activity of the CAR, of a cell expressing the CAR, or of a target cell. There is also provided a cell composition made by such a method and its use in the treatment of diseases such as cancer.

This disclosure relates to modified viruses, e.g., oncolytic vaccinia viruses, which have been modified to contain an exogenous nucleic acid that expresses a protein that modulates STAT3 activity. It is based, at least in part, on the discovery that vaccinia viruses modified to contain nucleic acid encoding PIAS3 and that express PIAS3 or a fragment thereof can inhibit STAT3 activity and enhance the anti-cancer activity of the vaccinia virus. Accordingly, this disclosure provides for oncolytic vaccinia viruses and methods of using them in the treatment of cancers.

The present disclosure provides a recombinant, probiotic lactic acid bacterium, wherein the bacterium comprises a non-replicating plasmid vector comprising (a) a tumor suppressor gene or anti-inflammatory gene operably linked to a first promoter that directs expression of the tumor suppressor gene or anti-inflammatory gene in a mammalian cell, and (b) an adhesin gene operably linked to a second promoter that directs expression of the adhesin gene in the bacterium. The present disclosure also provides uses of the recombinant bacterium, and methods of constructing the recombinant bacterium. The present disclosure also provides a method of treating cancer in a subject, wherein the method comprises administering a pharmaceutically effective amount of a recombinant, probiotic lactic acid bacterium, wherein the bacterium comprises a non-replicating plasmid vector comprising an adhesin gene operably linked to a promoter that directs expression of the adhesin gene in the bacterium.

The present invention relates to efficient methods for providing antigen-specific lymphoid cells. These lymphoid cells may be used to provide antigen specific T cell receptors having a defined MHC restriction and to identify immunologically relevant T cell epitopes. Furthermore, the present invention relates to antigen-specific T cell receptors and T cell epitopes and their use in immunotherapy.

The present invention provides compositions and methods for inhibiting PTPN22 for restoring human central B-cell tolerance or for treating or preventing an autoimmune disease or disorder.

Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

Disclosed herein are compounds having activity as cell penetrating peptides. In some examples, the compounds can comprise a cell penetrating peptide moiety and a cargo moiety. The cargo moiety can comprise one or more detectable moieties, one or more therapeutic moieties, one or more targeting moieties, or any combination thereof. In some examples, the cell penetrating peptide moiety is cyclic. In some examples, the cell penetrating peptide moiety and cargo moiety together are cyclic. In some examples, the cell penetrating peptide moiety is cyclic and the cargo moiety is appended to the cyclic cell penetrating peptide moiety structure. In some examples, the cargo moiety is cyclic and the cell penetrating peptide moiety is cyclic, and together they form a fused bicyclic system.

Provided is a composition for inhibiting, preventing, alleviating, or treating adipogenesis. Mesenchymal stem cells according to one aspect or a composition comprising the same inhibit fat accumulation or adipose tissue increase and thus may be advantageously utilized in the prevention, treatment, or alleviation of diseases associated with abnormal fat metabolism.

The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.