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

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 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.

Source: ScienceNOW - March 1, 2018 Category: Science Authors: Sockolosky, J. T., Trotta, E., Parisi, G., Picton, L., Su, L. L., Le, A. C., Chhabra, A., Silveria, S. L., George, B. M., King, I. C., Tiffany, M. R., Jude, K., Sibener, L. V., Baker, D., Shizuru, J. A., Ribas, A., Bluestone, J. A., Garcia, K. C. Tags: Immunology reports Source Type: news