| Autor: |
Makkouk A; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, 52242, USA., Joshi VB, Wongrakpanich A, Lemke CD, Gross BP, Salem AK, Weiner GJ |
| Jazyk: |
angličtina |
| Zdroj: |
The AAPS journal [AAPS J] 2015 Jan; Vol. 17 (1), pp. 184-93. Date of Electronic Publication: 2014 Oct 18. |
| DOI: |
10.1208/s12248-014-9676-6 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Full text from SpringerLink