The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The present invention relates, in part, to agents that bind CD8 and their use as therapeutic and diagnostic agents. The present invention further relates to pharmaceutical compositions comprising the CD8 binding agents and their use in the treatment of various diseases, including, for example, cancers.

The present invention relates, in part, to agents that bind CD8 and their use as therapeutic and diagnostic agents. The present invention further relates to pharmaceutical compositions comprising the CD8 binding agents and their use in the treatment of various diseases, including, for example, cancers.

Combination therapies that include (i) an immune cell that expresses a chimeric antigen receptor (CAR) or similar molecule and (ii) a compound that preserves or potentiates the in vivo actions of tumor necrosis factor alpha (TNFα) against cancer cells are described. The combination therapies result in the killing of antigen-negative cells in the vicinity of immunotherapy targeted-antigen-positive cells reducing the survivability of escape variants and providing other benefits.

Disclosed herein, inter alia, are compositions and methods of modulating macrophage activity. Provided is a method of treating a disease (e.g., a macrophage-associated disease, autoimmune disease, inflammatory disease, or a cancer of an organ in the intraperitoneal cavity), the method including intraperitoneally administering to a subject in need thereof a therapeutically effective amount of a nanoparticle composition or pharmaceutical composition. Provided is a silica nanoparticle non-covalently bound to a plurality of nucleic acids, wherein the silica nanoparticle has a net positive charge in the absence of the plurality of nucleic acids. Provided is a pharmaceutical composition including a nanoparticle composition as described herein, and a pharmaceutically acceptable excipient.

The invention relates to the field of immunology and immuno-oncology. More specifically, the invention relates to multi-specific and bi-specific cytokine and antibody derivatives capable of cell and/or tissue targeting to locally enhance the immune response and to reduce systemic toxicity.

A recombinant lentiviral vector containing a gene encoding a TRAIL protein and a CD protein; and a cell that is transfected with the lentivirus produced by using the vector. A host cell transfected with the recombinant lentivirus maintains a high cell proliferation rate and overexpresses a TRAIL protein and a CD protein. Thus, a mesenchymal stem cell transfected with the lentivirus may be usefully employed as a cell therapeutic agent.

The invention of the present disclosure provides a method for treating a viral infection in a recipient subject suffering from or at risk of a viral infection including administering to the recipient subject a pharmaceutical composition comprising a therapeutic amount of superactivated cytokine killer T cells (SCKTCs) and a pharmaceutically acceptable carrier, and mobilizing an immune response of the recipient subject to the viral pathogen. When tested in vitro, the SCKTCs are characterized by a predominant production of T.sub.H1 dominant cytokines including IFN-γ; an IFN-γ:IL-4 ratio of at least 500:1; and at least 50% killing of target A549 cells at an effector:target ratio of 20:1. The present disclosure further provides a method of preparing a pharmaceutical composition comprising an enriched population of superactivated cytokine killer T cells (SCKTCs) wherein pulsing steps with monocyte-derived dendritic cells (DCs) loaded with alpha-GalCer achieve at least an 80% pure population of SCKTCs without positive or negative cell separation methods.

The invention of the present disclosure provides a method for treating a viral infection in a recipient subject suffering from or at risk of a viral infection including administering to the recipient subject a pharmaceutical composition comprising a therapeutic amount of superactivated cytokine killer T cells (SCKTCs) and a pharmaceutically acceptable carrier, and mobilizing an immune response of the recipient subject to the viral pathogen. When tested in vitro, the SCKTCs are characterized by a predominant production of T.sub.H1 dominant cytokines including IFN-γ; an IFN-γ:IL-4 ratio of at least 500:1; and at least 50% killing of target A549 cells at an effector:target ratio of 20:1. The present disclosure further provides a method of preparing a pharmaceutical composition comprising an enriched population of superactivated cytokine killer T cells (SCKTCs) wherein pulsing steps with monocyte-derived dendritic cells (DCs) loaded with alpha-GalCer achieve at least an 80% pure population of SCKTCs without positive or negative cell separation methods.

The present invention relates to tumour necrosis factor (TNF) muteins with improved properties, and in particular to TNF muteins which are agonists of, and bind selectively to, tumour necrosis factor receptor 1 (TNFR1). Compositions comprising said TNF muteins, which may additionally comprise appropriate anticancer agents or imaging agents are provided. The use of the muteins of the invention in methods of treating or detecting a tumour are also provided. The invention also provides nucleic acids (e.g. vectors) encoding the TNF muteins and host cells comprising said nucleic acids.