Use of insulin-like growth factors with gamma-chain cytokines to induce homeostatic proliferation of lymphocytes
OwnerTodd Michael BRUSKO, Melanie SHAPIROinventors
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Abstract
Low-dose IL-2 has been proposed as a therapy to rectify regulatory T cell (Treg) fitness in type 1 diabetes (T1D). Identification of a combinatorial approach permits lower IL-2 dosing and avoids off-target effects. Insulin-like growth factor-1 (IGF1) is a hormone that promotes immunoregulation. Disclosed are methods that synergizes IGF1 with IL-2 to expand Tregs. In vivo IL-2+IGF1 treatment expands murine Tregs to a greater extent than either agent alone. IGF1+IL-2 treatment permits gene transfer in primary human Treg without the requirement for conventional activation stimuli, observing that IGF1+IL-2 maintains Treg naivety.
Claims45
A method for expansion of a naive lymphocyte population, the method comprising culturing the lymphocyte population under culture conditions that promote homeostatic expansion of the lymphocyte population, wherein the culture conditions comprise subjecting the population to growth factors IGF1 and common gamma chain.
A method for expansion of a naive regulatory T-Cell (Treg) population, the method comprising culturing the Treg population under culture conditions that promote homeostatic expansion of the Treg population, wherein the culture conditions comprise subjecting the population to growth factors IL-2 and IGF1.
A method for modifying a lymphocyte population, comprising transducing one or more vectors into one or more cells of the lymphocyte population during or prior to culturing the lymphocyte population under culture conditions that promote homeostatic expansion of the naïve lymphocyte population, wherein the culture conditions comprise subjecting the population to growth factors IGF1 and common gamma chain.
A method for treating autoimmune diseases in a subject in need, comprising administering IL-2 and IGF1 to the subject in need, wherein administering promotes homeostatic expansion of Tregs in vivo.
The method of claim 39, wherein IGF1 is administered twice a day. The method of any of claims 39-44, wherein IGF1 has a dose of 20 μg/kg to 40 μg/kg.
Dependencies are inferred from the claim text.