In Situ Tumor Vaccination with Nanoparticle Co-Delivering CpG and STAT3 siRNA to Effectively Induce Whole-Body Antitumor Immune Response

Worapol Ngamcherdtrakul, Moataz Reda, Molly A. Nelson, Ruijie Wang, Husam Y. Zaidan, Daniel S. Bejan, Ngoc Ha Hoang, Ryan S. Lane, Shiuh Wen Luoh, Sancy A. Leachman, Gordon B. Mills, Joe W. Gray, Amanda W. Lund, Wassana Yantasee

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number2100628
JournalAdvanced Materials
Volume33
Issue number31
DOIs
StatePublished - Aug 5 2021

Keywords

  • cancer immunotherapy
  • intratumoral therapy
  • melanoma
  • nanotechnology
  • translational research

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

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