Intrapulmonary Delivery of CpG Microparticles Eliminates Lung Tumors.

Abstract

CpG oligonucleotides (ODN) stimulate the innate immune system by triggering cells that express TLR9. The resulting response promotes tumor regression, an effect optimized by delivery of CpG ODN to the tumor site. This work examines the effect of instilling CpG ODN adsorbed onto polyketal microparticles (CpG-MP) into the lungs of mice with non-small cell lung cancer. Intrapulmonary delivery of CpG-MP improved ODN uptake and retention at the tumor site, thereby inducing a stronger Th1 response than systemically administered or unadsorbed CpG ODN. CpG-MP reversed the immunosuppression that characterized the tumor microenvironment by (i) decreasing the number of immunosuppressive Tregs and M2 macrophages while (ii) increasing the number of tumoricidal CD8(+) T cells and M1 macrophages. These effects promoted tumor regression and culminated in 82% permanent survival of mice with otherwise fatal Lewis lung cancer.

• Authors: Takashi Sato, Takeshi Shimosato, Atsuhisa Ueda, Yoshiaki Ishigatsubo, Dennis M Klinman
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 14 Issue 10 Pg. 2198-205 (Oct 2015) ISSN: 1538-8514 [Electronic] United States
• PMID: 26206336 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Antineoplastic Agents
• Capsules
• CpG ODN 1555
• Oligodeoxyribonucleotides

Topics

• Administration, Inhalation
• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics, pharmacology)
• Capsules
• Carcinoma, Lewis Lung (drug therapy, immunology, pathology)
• Carcinoma, Non-Small-Cell Lung (drug therapy, immunology, pathology)
• Drug Screening Assays, Antitumor
• Immunity, Innate (drug effects)
• Lung Neoplasms (drug therapy, immunology, pathology)
• Mice, Inbred C57BL
• Mice, Knockout
• Oligodeoxyribonucleotides (administration & dosage, pharmacokinetics, pharmacology)