Journal article
Biodegradable microparticles loaded with doxorubicin and CpG ODN for in situ immunization against cancer
The AAPS journal, Vol.17(1), pp.184-193
01/2015
DOI: 10.1208/s12248-014-9676-6
PMCID: PMC4287287
PMID: 25331103
Abstract
In situ immunization is based on the concept that it is possible to break immune tolerance by inducing tumor cell death in situ in a manner that provides antigen-presenting cells such as dendritic cells (DCs) with a wide selection of tumor antigens that can then be presented to the immune system and result in a therapeutic anticancer immune response. We designed a comprehensive approach to in situ immunization using poly(lactic-co-glycolic acid) (PLGA)-biodegradable microparticles (MPs) loaded with doxorubicin (Dox) and CpG oligodeoxynucleotides (CpG) that deliver Dox (chemotherapy) and CpG (immunotherapy) in a sustained-release fashion when injected intratumorally. Dox induces immunogenic tumor cell death while CpG enhances tumor antigen presentation by DCs. PLGA MPs allow their safe co-delivery while evading the vesicant action of Dox. In vitro, we show that Dox/CpG MPs can kill B and T lymphoma cells and are less toxic to DCs. In vivo, Dox/CpG MPs combined with antibody therapy to enhance and maintain the T cell response generated systemic immune responses that suppressed injected and distant tumors in a murine B lymphoma model, leading to tumor-free mice. The combination regimen was also effective at reducing T cell lymphoma and melanoma tumor burdens. In conclusion, Dox/CpG MPs represent an efficient and safe tool for in situ immunization that could provide a promising component of immunotherapy for patients with a variety of types of cancer.
Details
- Title: Subtitle
- Biodegradable microparticles loaded with doxorubicin and CpG ODN for in situ immunization against cancer
- Creators
- Amani Makkouk - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, 52242, USAVijaya B JoshiAmaraporn WongrakpanichCaitlin D LemkeBrett P Gross - University of IowaAliasger K SalemGeorge J Weiner
- Resource Type
- Journal article
- Publication Details
- The AAPS journal, Vol.17(1), pp.184-193
- DOI
- 10.1208/s12248-014-9676-6
- PMID
- 25331103
- PMCID
- PMC4287287
- NLM abbreviation
- AAPS J
- ISSN
- 1550-7416
- eISSN
- 1550-7416
- Publisher
- United States
- Grant note
- P30 ES005605 / NIEHS NIH HHS P50 CA97274 / NCI NIH HHS P30 CA086862 / NCI NIH HHS P50 CA097274 / NCI NIH HHS
- Language
- English
- Date published
- 01/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9983985893002771
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