Expansion of donor-unrestricted MAIT cells with enhanced cytolytic function suitable for TCR redirection

• DOI: 10.1172/jci.insight.140074
• Publication Date: 2021-02-09T17:20:55Z
• Authors: Tiphaine Parrot; Katie Healy; Caroline Boulouis; Michał J. Sobkowiak; Edwin Leeansyah; Soo Aleman; Antonio Bertoletti; Margaret Sällberg...; Johan K. Sandberg
• Keywords: Adoptive Cell Transfer

Progress in our understanding of MR1-restricted mucosa-associated invariant T (MAIT) cells has raised interest harnessing these for immunotherapy. The innate-like response characteristics, abundance the blood, donor-unrestricted nature, and tropism tissues make MAIT suitable candidates adoptive cell transfer therapies. However, reliable methods tools to utilize such approaches are lacking. Here, we established methodology efficient expansion human culture with high purity yield, while preserving their functional toward natural ligand increasing cytotoxic potential. cultured retained effector memory characteristics without signs terminal differentiation expressed a more diverse set chemokine receptors, potentially widening already broad tissue tropism. To investigate potential context outside main role controlling bacterial infection, engineered new TCR specificity mediate effective antiviral HLA class I–restricted function. In summary, developed robust enhanced cytolytic capacity engineering specificity. These findings form basis development as platform