Peptide antagonists of c-family cytokines, which is associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of c-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Traditional approaches to inhibiting c-cytokine activity involve raising neutralizing antibodies against each individual c-cytokine family member/receptor subunit. However, success has been limited and often multiple c-cytokine family members co-operate to cause the disease state. Combinatorial use of neutralizing antibodies raised against each factor is impractical and poses an increased risk of adverse immune reactions. The present embodiments overcome these shortcomings by utilizing peptide antagonists based on the consensus c-subunit binding site to inhibit c-cytokine activity. Such approach allows for flexibility in antagonist design. The disclosed peptides exhibit Simul-Block activity, inhibiting the activity of multiple c-cytokine family members.

The present disclosure provides a multivalent biomolecule comprising three or more covalently linked common -chain receptor cytokines (e.g., IL-2, IL-4, IL-7, IL-9, IL-15 or IL-21, or an immunologically active fragment thereof). In one embodiment, the common -chain receptor cytokines in the multivalent biomolecule are expressed as Fc fusion proteins with an IgG1 Fc. The multivalent biomolecule presented herein can be used to activate or suppress immune responses in a subject.

Embodiments relate to peptide antagonists of c-family cytokines, which is associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of c-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Traditional approaches to inhibiting c-cytokine activity involve raising neutralizing antibodies against each individual c-cytokine family member/receptor subunit. However, success has been limited and often multiple c-cytokine family members co-operate to cause the disease state. Combinatorial use of neutralizing antibodies raised against each factor is impractical and poses an increased risk of adverse immune reactions. The present embodiments overcome these shortcomings by utilizing peptide antagonists based on the consensus c-subunit binding site to inhibit c-cytokine activity. Such approach allows for flexibility in antagonist design. In several embodiments, peptides exhibit Simul-Block activity, inhibiting the activity of multiple c-cytokine family members.

This disclosure relates to recombinant proteins comprising a GM-CSF sequence and an interleukin sequence and nucleic acids related thereto. In certain embodiments, the disclosure relates to recombinant proteins comprises N-terminal sequences that are the result of improved production techniques and uses for treating or preventing autoimmune diseases such as multiple sclerosis and cancer.

Featured are recombinant adenoviruses and vectors thereof. In particular, the adenoviruses are simian (rhesus) adenoviruses having a low seroprevalence and high immunogenicity (when expressing, e.g., an antigenic polypeptide) relative to other adenoviruses and vectors thereof. Also featured are methods for producing the adenoviruses and methods of treatment of diseases by administering the adenoviral vector(s) to a subject (e.g., a human).

The present disclosure provides CAR regulatory T cells. Further provided herein are methods for treating cancer, such as a solid cancer, comprising administering an effective amount of CAR regulatory T cells.

Provided are methods for treating Alzheimer's Disease and/or ameliorating at least one symptom thereof. In some embodiments, the methods include administering to a. subject with AD an inhibitor of a clusterin biological activity, wherein the composition is administered via a route and in an amount sufficient to inhibit the clusterin biological activity to thereby treat the subject's. AD and/or ameliorate at least one symptom thereof. Also provided are methods for reducing and/or inhibiting myelin decay in a subject in need thereof and methods for inhibiting differentiation of oligodendrocyte progenitor cells (OPCs) to mature oligodendrocytes, the method comprising contacting the OPCs with a clusterin gene product or a functional fragment or derivative thereof.

Featured are recombinant adenoviruses and vectors thereof. In particular, the adenoviruses are simian (rhesus) adenoviruses having a low seroprevalence and high immunogenicity (when expressing, e.g., an antigenic polypeptide) relative to other adenoviruses and vectors thereof. Also featured are methods for producing the adenoviruses and methods of treatment of diseases by administering the adenoviral vector(s) to a subject (e.g., a human).

Disclosed herein are single chain dimeric cytokines having improved physiological activity over wild-type cytokine monomers. The single chain dimeric cytokines of the disclosure may be useful in the treatment of various diseases or disorders relating to inflammatory conditions or proliferative conditions. Also disclosed are delivery vectors or agents for delivering the single chain dimeric cytokines to a subject. Such delivery vectors or agents include cells, bacteria and bacteriophages.