Efficient recovery of potent tumour-infiltrating lymphocytes through quantitative immunomagnetic cell sorting

Abstract

Adoptive cell therapies require the recovery and expansion of highly potent tumour-infiltrating lymphocytes (TILs). However, TILs in tumours are rare and difficult to isolate efficiently, which hinders the optimization of therapeutic potency and dose. Here we show that a configurable microfluidic device can efficiently recover potent TILs from solid tumours by leveraging specific expression levels of target cell-surface markers. The device, which is sandwiched by permanent magnets, balances magnetic forces and fluidic drag forces to sort cells labelled with magnetic nanoparticles conjugated with antibodies for the target markers. Compared with conventional cell sorting, immunomagnetic cell sorting recovered up to 30-fold higher numbers of TILs, and the higher levels and diversity of the recovered TILs accelerated TIL expansion and enhanced their therapeutic potency. Immunomagnetic cell sorting also allowed us to identify and isolate potent TIL subpopulations, in particular TILs with moderate levels of CD39 (a marker of T-cell reactivity to tumours and T-cell exhaustion), which we found are tumour-specific, self-renewable and essential for the long-term success of adoptive cell therapies.