Compositions and methods for modulating gamma-c-cytokine activity

Abstract

Peptide antagonists of γc-family cytokines, Interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21 are described. The γc-cytokines are 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 γc-cytokine activity are valuable therapeutic, cosmetic agents and research tools. Traditional approaches to inhibiting γc-cytokine activity involve raising neutralizing antibodies against each individual γc-cytokine family member/receptor subunit. However, success has been limited and often multiple γc-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. To overcome these shortcomings, use of peptide antagonists based on the consensus γc-subunit binding site to inhibit γc-cytokine activity is provided. Such approach allows for flexibility in antagonist design. Peptides can exhibit Simul-Block activity, inhibiting the activity of multiple γc-cytokine family members.