Off-Target and Tumor-Specific Accumulation of Monocytes, Macrophages and Myeloid-Derived Suppressor Cells after Systemic Injection

Abstract

Solid tumors frequently coexist with a degree of local chronic inflammation. Recruited myeloid cells can therefore be considered as interesting vehicles for tumor-targeted delivery of therapeutic agents. Using in vivo imaging, the short-term accumulation of systemically injected monocytes, macrophages and myeloid-derived suppressor cells (MDSCs) was compared in mice bearing fat pad mammary carcinomas. Monocytes and macrophages demonstrated almost identical in vivo and ex vivo distribution patterns with maximal tumor-associated accumulation seen 48 hours after injection that remained stable over the 4-day follow-up period. However, a substantial accumulation of both cell types was also seen in the liver, spleen and lungs albeit decreasing over time in all three locations. The MDSCs exhibited a similar distribution pattern as the monocytes and macrophages, but demonstrated a better relative on-target fraction over time. Overall, our findings highlight off-target cell accumulation as a major obstacle in the use of myeloid cells as vehicles for therapeutic tumor-targeted agents and indicate that their short-term on-target accumulation is mainly of nonspecific nature.