The disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g. a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling. Typically, the fusion proteins further comprise an in vivo half-life extension element, which may be cleaved from the cytokine in the tumor microenvironment.

The present disclosure relates to IL12 receptor agonists with improved therapeutic profiles.

A pharmaceutical composition is described, which comprises proteins and an immune checkpoint inhibitor, wherein the proteins comprise a fusion protein, and the fusion protein comprises cytokines IL12, IL2, and GMCSF. A reagent kit is also described, which comprises the pharmaceutical composition. The pharmaceutical composition or the reagent kit may be used in preparing a medicament for treating a tumor.

This invention relates to the field of therapeutics. Most specifically, the invention provides methods of generating conditionally expressing vectors for one or more immuunomodulators under the control of a gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals. These vector may be provided to treat a variety of disorders, e.g., neoplastic disorders, through direct injection or through in vitro engineered cells, such as dendritic cells.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The use of anti-HPV immunogens and nucleic acid molecules that encode them for the treatment and prevention of RRP are disclosed. Pharmaceutical composition, recombinant vaccines comprising DNA plasmid and live attenuated vaccines are disclosed as well methods of inducing an immune response to treat or prevent RRP are disclosed.

The disclosure relates to methods and materials for treating cancer. For example, recombinant vaccinia viruses having the ability to direct the expression of membrane-bound IL-12 polypeptides on the surface of infected cells and methods for using such recombinant vaccinia viruses to treat cancer are provided. Specifically, the disclosure provides a recombinant vaccinia virus comprising a vaccinia virus genome comprising a nucleic acid encoding an IL-12p35 polypeptide sequence and an IL-12p40 polypeptide sequence, wherein one of the polypeptide sequences comprises a membrane anchoring polypeptide sequence.

Provided is application of chimeric antigen receptor (CAR)-modified T (CART) cells in preparing drugs for cancer treatment, the CART cells contain an artificially-introduced costimulatory signal transduction domain, and the CART cell does not contain an artificially-introduced first signal transduction domain.

Disclosed are methods for preparing mRNA and proteins from synthetic DNA.