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.

The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

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.

Genetically engineered bacteria, pharmaceutical compositions thereof, and methods of treating or preventing autoimmune disorders, inhibiting inflammatory mechanisms in the gut, and/or tightening gut mucosal barrier function are disclosed.

Genetically engineered bacteria, pharmaceutical compositions thereof, and methods of treating or preventing autoimmune disorders, inhibiting inflammatory mechanisms in the gut, and/or tightening gut mucosal barrier function are disclosed.

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.

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.

The present invention provides compositions and methods for treating cancer or a metastasis thereof in a subject. In some embodiments, the methods involve administering a composition comprising therapeutically effective amount of at least one immune stimulator to the subject. In some embodiments, a combination of at least two immune stimulators is used for the treatment. In some embodiments, the combination includes an alpha thymosin peptide and an additional immune stimulator, and/or optionally one or more additional anti-cancer agents.

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.