A Precision Engineered Interleukin-2 for Bolstering CD8+ T- and NK-cell Activity Without Eosinophilia and Vascular Leak Syndrome in Nonhuman Primates
Overview
Overview
Authors
Authors
Affiliations
Affiliations
Soon will be listed here.
Abstract
Significance: SAR-444245 (SAR'245, pegenzileukin) is an extended half-life IL-2 that targets effector CD8+ T and NK cells, with little effect on regulatory T cells. We show that in the nonhuman primate model that closely approximates human immune function and response to IL-2, SAR'245 selectively activates CD8+ T and NK effectors without significant serious side effects (vascular leak syndrome or cytokine release syndrome), suggesting its potential for the treatment of solid tumors in humans.
References
1.
Charych D, Hoch U, Langowski J, Lee S, Addepalli M, Kirk P
. NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models. Clin Cancer Res. 2016; 22(3):680-90.
DOI: 10.1158/1078-0432.CCR-15-1631.
View
2.
Schanen B, Drake 3rd D
. A novel approach for the generation of human dendritic cells from blood monocytes in the absence of exogenous factors. J Immunol Methods. 2008; 335(1-2):53-64.
DOI: 10.1016/j.jim.2008.02.021.
View
3.
Krieg C, Letourneau S, Pantaleo G, Boyman O
. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci U S A. 2010; 107(26):11906-11.
PMC: 2900642.
DOI: 10.1073/pnas.1002569107.
View
4.
Melssen M, Lindsay R, Stasiak K, Rodriguez A, Briegel A, Cyranowski S
. Differential Expression of CD49a and CD49b Determines Localization and Function of Tumor-Infiltrating CD8 T Cells. Cancer Immunol Res. 2021; 9(5):583-597.
PMC: 8102369.
DOI: 10.1158/2326-6066.CIR-20-0427.
View
5.
Locker G, Kapiotis S, Veitl M, Mader R, Stoiser B, Kofler J
. Activation of endothelium by immunotherapy with interleukin-2 in patients with malignant disorders. Br J Haematol. 1999; 105(4):912-9.
DOI: 10.1046/j.1365-2141.1999.01453.x.
View