Authors: Hannah M. Knochelmann, Connor J. Dwyer, Aubrey S. Smith, Jacob S. Bowers, Megan M. Wyatt, Michelle H. Nelson, Guillermo O. Rangel Rivera, Joshua D. Horton, Carsten Krieg, Kent Armeson, Gregory B. Lesinski, Mark P. Rubinstein, Zihai Li, Chrystal M. Paulos
Summary: The accessibility of adoptive T-cell transfer therapies (ACT) is hindered by the cost and time required for product development. Here we describe a streamlined ACT protocol using Th17 cells expanded only 4 days ex vivo. While shortening expansion compromised cell yield, this method licensed Th17 cells to eradicate large tumors to a greater extent than cells expanded longer term. Day 4 Th17 cells engrafted, induced release of multiple cytokines including IL6, IL17, MCP-1, and GM-CSF in the tumor-bearing host, and persisted as memory cells. IL6 was a critical component for efficacy of these therapies via its promotion of long-term immunity and resistance to tumor relapse. Mechanistically, IL6 diminished engraftment of FoxP3+ donor T cells, corresponding with robust tumor infiltration by donor effector over regulatory cells for the Day 4 Th17 cell product relative to cell products expanded longer durations ex vivo. Collectively, this work describes a method to rapidly generate therapeutic T-cell products for ACT and implicates IL6 in promoting durable immunity of Th17 cells against large, established solid tumors.
Source: Cancer Research, 2020; 80 (18): 3920