Stable conjugation of nanoparticles (NPs) to the surfaces of T cells and HSCs via cell-surface thiols.
New Scientist – Immune cells called cytotoxic T-cells swarm over and demolish cancerous cells inside the body. Unfortunately, many tumours emit a mysterious chemical cocktail to weaken any T-cells that swim too close.
While investigating how to increase T-cells’ ability to attack tumours, Irvine’s team found they could fasten 100 nanoparticle capsules to a single T-cell without impairing its function – capsules they could fill with any number of drugs. Irvine’s team filled the nanoparticle capsules with interleukins – molecules naturally produced by the immune system that give T-cells chemical encouragement to keep on fighting. When they injected these into mice with bone and lung cancer, the T-cells not only swarmed over the tumours but stayed active far longer than T-cells with empty capsules.
What’s more, mice injected with unmodified T-cells died from their tumours within 30 days, whereas mice that received T-cells armed with interleukin were still alive and improving in health a month later.
A major limitation of cell therapies is the rapid decline in viability and function of the transplanted cells. Here we describe a strategy to enhance cell therapy via the conjugation of adjuvant drug–loaded nanoparticles to the surfaces of therapeutic cells. With this method of providing sustained pseudoautocrine stimulation to donor cells, we elicited marked enhancements in tumor elimination in a model of adoptive T cell therapy for cancer. We also increased the in vivo repopulation rate of hematopoietic stem cell grafts with very low doses of adjuvant drugs that were ineffective when given systemically. This approach is a simple and generalizable strategy to augment cytoreagents while minimizing the systemic side effects of adjuvant drugs. In addition, these results suggest therapeutic cells are promising vectors for actively targeted drug delivery.
Lipid-coated NPs used in surface conjugation studies. Shown are schematic views (upper panels) and cryoEM images (lower panels, scale bars, 100 nm) of liposomes (a), stable multilamellar lipid NPs (b), and lipid-coated poly (lactide-co-glyolide) (PLGA) particles (c) used for cell conjugation..