Plasma Exchange May Enhance Antitumor Effects by Removal of Soluble Programmed Death-Ligand 1 and Extracellular Vesicles: Preliminary Study

Abstract

The antitumor effect of antibody-drug conjugates (ADC) is the main factor in achieving cures. Although the mechanism of tumor resistance to treatment is multifaceted, tumor-derived extracellular vesicles (T-EVs) have been implicated as contributing to the attenuation of ADC therapeutic efficacy. Thus, strategies to eliminate T-EVs are highly promising for overcoming drug resistance. Here we demonstrate plasma exchange therapy to remove T-EVs, decreasing their amount in vitro by 75%. Although trastuzumab emtansine (T-DM1) treatment alone was effective in our rat tumor model, the combination therapy of T-DM1 and T-EV filtration achieved early tumor shrinkage. Our results indicate that T-EV filtration plus ADC is a promising strategy for overcoming drug resistance.

Keywords

• antibody-drug conjugate
• extracellular vesicles
• plasma exchange
• trastuzumab emtansine