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 invention is directed at a medicament comprising a combination of dehydrated or cryopreserved amniotic membrane isolated from human or other mammalian placenta, wherein the amniotic membrane is in a form of a sheet or a sheet composite comprising multiple overlain sheets of amniotic membrane; and umbilical cord blood serum, isolated from umbilical cord blood of a human or other mammal, separately of each other, for combined use in a method of treating a tissue wound in a human or other mammalian subject by applying the amniotic membrane to injured tissue of the wound to contact injured tissue of the wound and contacting the amniotic membrane with the umbilical cord blood serum.

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.

Cancer is treated via a coordinated treatment regimen that use various compounds and compositions that employ prime-boost vaccination in combination with immune modulatory treatment and biasing of an immune response towards a Th1 profile.

Cancer is treated via a coordinated treatment regimen that use various compounds and compositions that employ prime-boost vaccination in combination with immune modulatory treatment and biasing of an immune response towards a Th1 profile.

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 provides for the intratumoral delivery of immunomodulators. In particular, it provides delivery of co-stimulatory molecules using intratumoral electroporation. The present invention provides a method for the treatment of malignancies, wherein the administration of a plasmid encoding for a therapeutic costimulatory protein, in combination with electroporation has a therapeutic effect on primary tumors as well as distant tumors and metastases.

The present invention provides for the intratumoral delivery of at least one immunostimulatory cytokine in combination with at least one checkpoint inhibitor. In particular, it provides delivery of a plasmid encoding the immunostimulatory cytokine using intratumoral electroporation. The checkpoint inhibitor may be administered systemically or encoded on a plasmid and delivered using intratumoral electroporation. The checkpoint inhibitor may be delivered contemporaneously with or after treatment with the immunomodulatory cytokine.

Cancer is treated via a coordinated treatment regimen that use various compounds and compositions that employ a combination vaccination together with immune modulatory treatment and biasing of an immune response towards a Th1 profile.

Combination therapy of a cancer with a multi-specific binding protein that bind a tumor associated antigen, the NKG2D receptor, and CD16, in combination with a second anti-cancer agent are described. Also described are pharmaceutical compositions of the multi-specific binding protein, and therapeutic methods useful for the treatment of cancer in combination with a second anti-cancer agent.