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 nucleic acids.

This disclosure relates to modified immunoglobulins.

The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells. In some embodiments, the methods include reaction mixtures, and resulting cell formulations, that are created using whole blood, or a component thereof that is not a PBMC, and additionally comprise T cells and recombinant retroviral particles having polynucleotides that encode a CAR. In some embodiments, modified lymphocytes are reintroduced into a subject subcutaneously. In some embodiments, polynucleotides that provide T cells the ability to regulate cell survival and proliferation in response to binding to a CAR, are provided.

The present invention relates to a pharmaceutical composition comprising an immunoglobulin Fc region and an IL-7 fusion protein. Specifically, when a fusion protein comprising the immunoglobulin Fc region and IL-7 is administered to an affected area, a strong immune response is induced in the body and thus allows human papillomavirus-caused diseases to be prevented or treated.

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.

Provided are activatable proprotein or procytokine homodimers composed of at least two separate polypeptide chains, each chain comprising a binding moiety such as an Fc region, a cytokine, a cytokine receptor, and at least one a cleavable linker, among other optional features, and related pharmaceutical compositions and methods of use thereof.

Provided is a pharmaceutical formulation comprising a modified IL-7 protein. More particularly, it comprises (a) a modified IL-7 fusion protein; (b) a basal buffer with a concentration of 10 to 50 mM; (c) a sugar with a concentration of 2.5 to 5 w/v %; and (d) a surfactant with a concentration of 0.05 to 6 w/v %. Such pharmaceutical formulation of a modified IL-7 fusion protein does not show aggregates formation, but shows protective effects on proteins under stress conditions such as oxidation or agitation, and thus can effectively be used for the treatment of a patient.

The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.

Provided is a cytokine combination for treating a tumor and/or preventing recurrence or metastasis of the tumor. The cytokine combination comprising at least three cytokines selected from the following groups: IL(interleukin)12 or a functional variant thereof, GMCSF (granulocyte-macrophage colony-stimulating factor) or a functional variant thereof, FLT3L (FMS-like tyrosine kinase 3 ligand) or a functional variant thereof, IL2 or a functional variant thereof, IL15 or a functional variant thereof, IL21 or a functional variant thereof, and IL7 or a functional variant thereof. Also provided is a nucleic acid molecule encoding the cytokine combination and a vector thereof, a cell, a pharmaceutical composition, and a application thereof for the manufacture of a drug for treating the tumor and/or preventing recurrence or metastasis of the tumor.

An exemplary combination drug includes (a1) an immunoresponsive cell expressing interleukine-7, CCL19, and a cell surface molecule that specifically recognizes a cancer antigen or (a2) one or more kinds of cells, one or more kinds of nucleic acid delivery vehicles, or a combination thereof, which cooperatively include a nucleic acid encoding interleukine-7 and a nucleic acid encoding CCL19; and (b) an immunosuppression inhibitor, and the drug is for use in treatment of a cancer in a subject. An exemplary immunoresponsive cell expresses interleukin-7, CCL19, an immunosuppression inhibiting polypeptide, and a cell surface molecule that specifically recognizes a cancer antigen.