In certain embodiments, this disclosure relates to conjugates comprising GM-CSF and IL-7 and uses related thereto, e.g., enhancing the adaptive immune system. Typically the GM-CSF and IL-7 are connected by a polymer linker, e.g., polypeptide. In certain embodiments, the disclosure relates to nucleic acids encoding these polypeptide conjugates, vectors comprising nucleic acid encoding polypeptide conjugates, and protein expression systems comprising these vectors such as infectious viral particles and host cells comprising such a nucleic acids.

Provided herein are methods and compositions useful for treating cancer, such as prostate cancer, through adoptive cell transfer of T cells derived from patients and genetically engineered to express MDA-7/IL-24 and/or other immune modulating agents. The methods described herein result in cancer cell death and reprogramming of the tumor immune compartment to restore antitumor immunity both at a primary tumor site and systemically.

Compositions and methods for NK cell based treatments, and particularly NK cells that express and intracellularly retain IL-2, are presented in which the NK cells are stimulated with a chimeric protein that has a cancer cell targeting portion and an IL-12 portion. Beneficially, such chimeric protein has substantially reduced systemic toxicity and induces IFN-? secretion in a targeted manner. Moreover, chimeric proteins contemplated herein also significantly enhanced IFN-? secretion in NK cells that express and intracellularly retain IL-2 as compared to native NK cells. Preferred chimeric proteins comprise SEQ ID NO:1 or SEQ ID NO:2, and SEQ ID NO:3.

Provided herein are compositions and methods for the treatment of cancers using modified TILs, wherein the modified TILs include one or more immunomodulatory agents (e.g. cytokines) associated with their cell surface. The immunomodulatory agents associated with the TILs provide a localized immunostimulatory effect that can advantageously enhance TIL survival, proliferation and/or anti-tumor activity in a patient recipient. As such, the compositions and methods disclosed herein provide effective cancer therapies.

B cell subsets, generation of B cell subsets and utilization of B cell subsets for treatment of Chronic Obstructive Pulmonary Disease (COPD). In one embodiment B cells possessing a B regulatory phenotype are generated in vivo by administrating of mesenchymal stem cells. In another embodiment B regulatory cells are utilized to treat COPD in an interleukin-35 dependent manner. In another embodiment B regulatory cells possess the marker CD5 and produce interleukin-10.

The present disclosure relates to IL2 agonists with improved therapeutic profiles.

Provided herein are T-cell receptor (TCR) fusion proteins (TFPs), T-cells engineered to express one or more TFPs, and methods of use thereof for the treatment of diseases, including cancer.

This invention relates to the field of therapeutics. Most specifically invention provides methods of generating in vitro engineered immune cells conditionally expressing interleukin-12 (IL-12) and one or more immunomodulators under the control of a gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals.

In certain embodiments, this disclosure relates to conjugates comprising GM-CSF and IL-7 and uses related thereto, e.g., enhancing the adaptive immune system. Typically the GM-CSF and IL-7 are connected by a polymer linker, e.g., polypeptide. In certain embodiments, the disclosure relates to nucleic acids encoding these polypeptide conjugates, vectors comprising nucleic acid encoding polypeptide conjugates, and protein expression systems comprising these vectors such as infectious viral particles and host cells comprising such a nucleic acids.

Disclosed is a method for labeling, detecting and/or isolating Foxp3+ Treg cells from a biological sample containing peripheral blood mononuclear cells (PBMC) or lymphocytes including the following steps of: (i) coupling the surface of PBMC or lymphocytes to a capture moiety which binds to the cell through a cell surface molecule and to interleukin-34 (IL34), (ii) culturing the lymphocytes under conditions wherein IL34 is secreted, released and specifically captured by the capture moiety, (iii) labeling the IL34 expressing lymphocytes with a label moiety, and (iv) optionally detecting and/or isolating the IL34 expressing lymphocytes which are Foxp3+ Treg cells. Also disclosed is an isolated population of Foxp3+ Treg cells obtainable by the method and uses thereof.