期刊
ADVANCED MATERIALS
卷 33, 期 31, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202100628
关键词
cancer immunotherapy; intratumoral therapy; melanoma; nanotechnology; translational research
类别
资金
- 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
- OHSU Center for Women's Health Circle of Giving Award
The study introduces a widely applicable approach to enhance the efficacy of ICIs through intratumoral administration of the AIRISE-02 nanotherapeutic, showing regression of tumors and long-term memory immune effect. This approach is effective in breast and colon tumor models, and well tolerated in mice and nonhuman primates.
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.
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