Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes.

ABSTRACT: Interleukin-2 (IL-2) is a cytokine required for effector T cell expansion, survival, and function, especially for engineered T cells in adoptive cell immunotherapy, but its pleiotropy leads to simultaneous stimulation and suppression of immune responses as well as systemic toxicity, limiting its therapeutic use. We engineered IL-2 cytokine-receptor orthogonal (ortho) pairs that interact with one another, transmitting native IL-2 signals, but do not interact with their natural cytokine and receptor counterparts. Introduction of orthoIL-2Rβ into T cells enabled the selective cellular targeting of orthoIL-2 to engineered CD4⁺ and CD8⁺ T cells in vitro and in vivo, with limited off-target effects and negligible toxicity. OrthoIL-2 pairs were ef

SUBMITTER: Sockolosky JT 

PROVIDER: S-EPMC5947856 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature