Therapeutic cell engineering with surface-conjugated synthetic nanoparticles.

Abstract

A major limitation of cell therapies is the rapid decline in viability and function of 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. Using this method to provide sustained pseudo-autocrine stimulation to donor cells, we elicited dramatic enhancements in tumor elimination in a model of adoptive T-cell therapy for cancer and increased the in vivo repopulation rate of hematopoietic stem cell grafts, using very low doses of adjuvant drugs that were ineffective when given systemically. This approach is a facile and generalizable strategy to augment cytoreagents while minimizing systemic side effects of adjuvant drugs. In addition, these results suggest therapeutic cells are promising vectors for actively targeted drug delivery.