@article{f1886687fddd447bac5cbc6d2dd6a3e6,
title = "In Situ Tumor Vaccination with Nanoparticle Co-Delivering CpG and STAT3 siRNA to Effectively Induce Whole-Body Antitumor Immune Response",
abstract = "The success of immunotherapy with immune checkpoint inhibitors (ICIs) in a subset of individuals has been very exciting. However, in many cancers, responses to current ICIs are modest and are seen only in a small subsets of patients. Herein, a widely applicable approach that increases the benefit of ICIs is reported. Intratumoral administration of augmenting immune response and inhibiting suppressive environment of tumors—AIRISE-02 nanotherapeutic that co-delivers CpG and STAT3 siRNA—results in not only regression of the injected tumor, but also tumors at distant sites in multiple tumor model systems. In particular, three doses of AIRISE-02 in combination with systemic ICIs completely cure both treated and untreated aggressive melanoma tumors in 63% of mice, while ICIs alone do not cure any mice. A long-term memory immune effect is also reported. AIRISE-02 is effective in breast and colon tumor models as well. Lastly, AIRISE-02 is well tolerated in mice and nonhuman primates. This approach combines multiple therapeutic agents into a single nanoconstruct to create whole-body immune responses across multiple cancer types. Being a local therapeutic, AIRISE-02 circumvents regulatory challenges of systemic nanoparticle delivery, facilitating rapid translation to the clinic. AIRISE-02 is under investigational new drug (IND)-enabling studies, and clinical trials will soon follow.",
keywords = "cancer immunotherapy, intratumoral therapy, melanoma, nanotechnology, translational research",
author = "Worapol Ngamcherdtrakul and Moataz Reda and Nelson, {Molly A.} and Ruijie Wang and Zaidan, {Husam Y.} and Bejan, {Daniel S.} and Hoang, {Ngoc Ha} and Lane, {Ryan S.} and Luoh, {Shiuh Wen} and Leachman, {Sancy A.} and Mills, {Gordon B.} and Gray, {Joe W.} and Lund, {Amanda W.} and Wassana Yantasee",
note = "Funding Information: This work was funded by the Wayne D. Kuni and Joan E. Kuni Foundation, National Cancer Institute R44CA217534, National Center for Advancing Translational Sciences R43TR001906, OHSU Knight Cancer Institute's Hillcrest Committee Pilot Award, and OHSU Center for Women's Health Circle of Giving Award. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH and US government. The authors would like to thank Dr. Michael Templin and Dr. Melinda Tyner of Charles River Laboratory and their team for assistance in designing and executing primate studies along with data interpretation. The authors thank Dr. Zachary Hartman of Duke University for the MM3MG‐HER2Δ16 cell line and providing advice on the breast tumor model for immunotherapeutic testing. The authors appreciate Dr. Jeremy Heidel for his advice on Chemistry, Manufacturing, and Control (CMC) strategies. The authors thank Freda Hu for the assistance with the artwork and compiling primate's data, and Alyssa Carlson for assistance with NP count measurement. The authors appreciate OHSU's Flow Cytometry Shared Resource, Histopathology Core, and Elemental Analysis Core. Lastly, the authors would like to thank Dr. Zheng Xia of OHSU's Department of Molecular Microbiology and Immunology for his independent reviewing of the data in this manuscript as required by OHSU's conflict of interest guidelines. Funding Information: This work was funded by the Wayne D. Kuni and Joan E. Kuni Foundation, National Cancer Institute R44CA217534, National Center for Advancing Translational Sciences R43TR001906, OHSU Knight Cancer Institute's Hillcrest Committee Pilot Award, and OHSU Center for Women's Health Circle of Giving Award. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH and US government. The authors would like to thank Dr. Michael Templin and Dr. Melinda Tyner of Charles River Laboratory and their team for assistance in designing and executing primate studies along with data interpretation. The authors thank Dr. Zachary Hartman of Duke University for the MM3MG-HER2?16 cell line and providing advice on the breast tumor model for immunotherapeutic testing. The authors appreciate Dr. Jeremy Heidel for his advice on Chemistry, Manufacturing, and Control (CMC) strategies. The authors thank Freda Hu for the assistance with the artwork and compiling primate's data, and Alyssa Carlson for assistance with NP count measurement. The authors appreciate OHSU's Flow Cytometry Shared Resource, Histopathology Core, and Elemental Analysis Core. Lastly, the authors would like to thank Dr. Zheng Xia of OHSU's Department of Molecular Microbiology and Immunology for his independent reviewing of the data in this manuscript as required by OHSU's conflict of interest guidelines. Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH",
year = "2021",
month = aug,
day = "5",
doi = "10.1002/adma.202100628",
language = "English (US)",
volume = "33",
journal = "Advanced Materials",
issn = "0935-9648",
publisher = "Wiley-VCH Verlag",
number = "31",
}