Evaluating IL-2 Variants in PD-1 Therapy

For comparing IL-2(WT) and IL-2(V) combination therapies, recombinant human IL-2(WT) or IL-2(V), and anti-mouse PD-L1 antibody with DAPG mutation were produced and provided by Roche as previously described^{37 (link)}. For PD-1 monotherapy, 200 μg of anti-mouse PD-L1 antibody (Roche) or mouse IgG1 isotype control (MOPC-21, BioXCell) was administered into LCMV chronically infected mice every 3 days for 2 weeks. For the combination therapy, IL-2(WT) or IL-2(V) therapy was combined with PD-1 therapy, where 1 μg of IL-2(WT) (Roche) or 10 μg of IL-2(V) (Roche) diluted in PBS with 0.1% normal mouse serum was given i.p. twice daily for 2 weeks. In chronic infection model with LCMV-specific CD4⁺ T cells, IL-2(WT) and IL-2(V) was given i.p. once daily from day 25 to day 33 after mice were infected with LCMV clone 13.

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Hashimoto M., Araki K., Cardenas M.A., Li P., Jadhav R.R., Kissick H.T., Hudson W.H., McGuire D.J., Obeng R.C., Wieland A., Lee J., McManus D.T., Ross J.L., Im S.J., Lee J., Lin J.X., Hu B., West E.E., Scharer C.D., Freeman G.J., Sharpe A.H., Ramalingam S.S., Pellerin A., Teichgräber V., Greenleaf W.J., Klein C., Goronzy J.J., Umaña P., Leonard W.J., Smith K.A, & Ahmed R. (2022). PD-1 combination therapy with IL-2 modifies CD8+ T cell exhaustion program. Nature, 610(7930), 173-181.

Publication 2022

anti-mouse PD-L1 antibody MOPC-21

Anti antibody Cd4 t cells Chronic infection Clone Combination therapy Combined therapy Igg1 Isotype Lcmv Mice Mutation Pd l1 Recombinant human il 2 Serum Therapy

Corresponding Organization : Emory University

Other organizations : Cincinnati Children's Hospital Medical Center, University of Cincinnati Medical Center, National Heart Lung and Blood Institute, National Institutes of Health, Stanford University, Mayo Clinic, WinnMed, Northwestern University, The Ohio State University, Sungkyunkwan University, Harvard University, Dana-Farber Cancer Institute, Boston VA Research Institute, Brigham and Women's Hospital, Biogen (United States), Roche (Switzerland), Cornell University

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Variable analysis

independent variables

Type of IL-2 therapy: IL-2(WT) or IL-2(V)
PD-1 therapy: Anti-mouse PD-L1 antibody or mouse IgG1 isotype control

dependent variables

LCMV-specific CD4+ T cell response

control variables

Chronic LCMV infection model
Route of administration (i.p.)
Dosage and frequency of IL-2(WT) and IL-2(V) therapy
Duration of therapy (2 weeks for PD-1 and combination therapies, 8 days for chronic infection model)

controls

Positive control: Anti-mouse PD-L1 antibody
Negative control: Mouse IgG1 isotype control

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