High Capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of Lung Adenocarcinoma

Vinod, N.; Hwang, D.; Azam, S. H.; Van Swearingen, A. E. D.; Wayne, E.; Fussell, S. C.; Sokolsky-Papkov, M.; Pecot, C. V.; Kabanov, A. V.

doi:10.1101/2019.12.12.874198

bioRxiv · 10.1101/2019.12.12.874198

High Capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of Lung Adenocarcinoma

Vinod, N.·Hwang, D.·Azam, S. H.·Van Swearingen, A. E. D.·Wayne, E.·Fussell, S. C.·Sokolsky-Papkov, M.·Pecot, C. V.·Kabanov, A. V.

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Abstract

About 40% of the NSCLC patients 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-PD1 checkpoint blockade have shown promise; however, response to such strategies is highly variable across patients. Here, we show that our novel poly(2-oxazoline) (POx) based nanomicellar formulation of Resiquimod, an imidazoquinoline TLR 7/8 agonist, had a superior tumor inhibitory effect in a metastatic model of lung adenocarcinoma, relative to anti-PD1 immune checkpoint blockade therapy as well as platinum-based chemotherapy, which is the mainstay of treatment for NSCLC. Investigation of the in vivo immune status following Resiquimod PM (POx micellar formulation of Resiquimod) treatment showed that Resiquimod-based stimulation of antigen-presenting cells in the tumor microenvironment resulted in the mobilization of anti-tumor CD8+ immune response. Our study demonstrates the promise of optimally delivered and nano-formulated Resiquimod as a new immunomodulating therapeutic strategy for the treatment of metastatic NSCLC.

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Vinod, N., Hwang, D., Azam, S. H., Van Swearingen, A. E. D., Wayne, E., Fussell, S. C., Sokolsky-Papkov, M., Pecot, C. V., Kabanov, A. V.. 2019-12-12. High Capacity poly(2-oxazoline) formulation of TLR 7/8 agonist extends survival in a chemo-insensitive, metastatic model of Lung Adenocarcinoma. https://doi.org/10.1101/2019.12.12.874198

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