1. High-capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of lung adenocarcinoma
- Author
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Alexander V. Kabanov, Chad V. Pecot, Marina Sokolsky-Papkov, Sloane Christian Fussell, Salma H. Azam, Elizabeth Wayne, Duhyeong Hwang, Natasha Vinod, and Amanda E.D. Van Swearingen
- Subjects
Lung Neoplasms ,medicine.medical_treatment ,Adenocarcinoma of Lung ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Adjuvants, Immunologic ,Carcinoma, Non-Small-Cell Lung ,Tumor Microenvironment ,medicine ,Humans ,Health and Medicine ,Oxazoles ,Research Articles ,Cancer ,030304 developmental biology ,0303 health sciences ,Chemotherapy ,Tumor microenvironment ,Multidisciplinary ,business.industry ,SciAdv r-articles ,Immunotherapy ,respiratory system ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Immune checkpoint ,Imidazoquinoline ,Toll-Like Receptor 7 ,chemistry ,Toll-Like Receptor 8 ,030220 oncology & carcinogenesis ,Cancer research ,Adenocarcinoma ,Resiquimod ,business ,Research Article - Abstract
Polymeric micelle formulation of an immune modulator improves survival in a highly aggressive model of non–small cell lung cancer., 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.
- Published
- 2020