High-capacity Poly(2-oxazoline) Formulation of TLR 7/8 Agonist Extends Survival in a Chemo-insensitive, Metastatic Model of Lung Adenocarcinoma

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 Jun 30

PMID 32596460

Citations 29

Authors

Natasha Vinod

Duhyeong Hwang

Salma H Azam

Amanda E D Van Swearingen

Elizabeth Wayne

Sloane Christian Fussell

Marina Sokolsky-Papkov

Chad V Pecot

Alexander V Kabanov

Affiliations

Soon will be listed here.

Abstract

About 40% of patients with non-small cell lung cancer (NSCLC) have stage IV cancer at the time of diagnosis. The only viable treatment options for metastatic disease are systemic chemotherapy and immunotherapy. Nonetheless, chemoresistance remains a major cause of chemotherapy failure. New immunotherapeutic modalities such as anti-PD-1 immune checkpoint blockade have shown promise; however, response to such strategies is highly variable across patients. Here, we show that our unique poly(2-oxazoline)-based nanomicellar formulation (PM) of Resiquimod, an imidazoquinoline Toll-like receptor (TLR) 7/8 agonist, had a superior tumor inhibitory effect in a metastatic model of lung adenocarcinoma, relative to anti-PD-1 therapy or platinum-based chemotherapy. Investigation of the in vivo immune status following Resiquimod PM treatment showed that Resiquimod-based stimulation of antigen-presenting cells in the tumor microenvironment resulted in the mobilization of an antitumor CD8 immune response. Our study demonstrates the promise of poly(2-oxazoline)-formulated Resiquimod for treating metastatic NSCLC.

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