Science Sub-Journal: Human Orthogonal IL-2/IL-2Rβ System Enhances the Proliferation and Antitumor Effects of CAR-T Cells

March 8, 2022 / Bio Valley BIOON/--- Interleukin-2 (IL-2) is a crucial T cell cytokine that promotes T cell proliferation and effector function, and is considered a therapeutic a method for cancer; however, systemic administration of IL-2 often results in severe toxic side effects, which limits its application in enhancing CAR-T cell immunotherapy

In a new study, researchers from the Perelman School of Medicine at the University of Pennsylvania and the Stanford University School of Medicine designed a pair of human orthogonal IL-2 (ortho-hIL-2) and human Orthogonal IL-2Rβ (ortho-hIL-2Rβ) pair containing human-specific mutations

T cells, image via CC0 Public Domain

T cells are genetically engineered to express the receptor ortho-hIL-2Rβ, which can only be activated by ortho-hIL-2

Using CAR-T cells that specifically target CD19, these authors found that ortho-hIL-2 induced ortho-hIL-2Rβ-positive CAR-T cells 2 weeks after adoptive transfer into immunodeficient mice bearing CD19+ Nalm6 leukemia xenografts Dose-dependent increase of T cell proliferation in vivo by up to 1000-fold

Ortho-hIL-2 can rescue the anti-leukemia effect of an unsatisfactory CAR-T cell dose

References:

Qian Zhang et al.