Publication Date:
2018-03-06
Description:
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 ortho IL-2Rβ into T cells enabled the selective cellular targeting of ortho IL-2 to engineered CD4 + and CD8 + T cells in vitro and in vivo, with limited off-target effects and negligible toxicity. Ortho IL-2 pairs were efficacious in a preclinical mouse cancer model of adoptive cell therapy and may therefore represent a synthetic approach to achieving selective potentiation of engineered cells.
Keywords:
Immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Geosciences
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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