A single dose of heated chemo-immunotherapy for long-term tumor inhibition

Abstract

The high primary resistance and the following adaptive resistance to therapeutic PD-1/PD-L1 pathway blockade have limited their clinical outcomes. Here, we reported the development of PMJ NPs, the biodegradable nanoparticles for the co-delivery of mitoxantrone (MTO, both chemo drug and photothermal agent) and JQ1 (PD-L1 inhibitor) to achieve mild heated chemotherapy to potentiate anti-PD therapy. Therapeutic regimens of PMJ NPs-based chemo-immunotherapy demonstrated a tumor suppression at early treatment stage but resulted in tumor recurrence later on, and was accompanied by the upregulation of the alternative immune checkpoints for adaptive resistance performance. However, we proved that mild heat (43 ℃) combined therapy led to the enduring tumor remission in both 4T1 and A20 tumor models with only single dose of PMJ NPs. The extra mild heat treatment was confirmed to play a key role for enhanced tumor immunotherapy. Our work provided the single dose of heated chemo-immunotherapy to achieve the long-term tumor suppression might offer a promising regimen for various tumors inhibition in clinics.