Biodegradable microparticles loaded with doxorubicin and CpG ODN for in situ immunization against cancer

AAPS J. 2015 Jan;17(1):184-93. doi: 10.1208/s12248-014-9676-6. Epub 2014 Oct 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacology*
  • Delayed-Action Preparations
  • Dendritic Cells / immunology
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacology*
  • Female
  • Immunotherapy / methods
  • Lactic Acid / chemistry*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy
  • Lymphoma, T-Cell / immunology
  • Lymphoma, T-Cell / pathology
  • Lymphoma, T-Cell / therapy
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma / therapy
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microspheres
  • Oligodeoxyribonucleotides / administration & dosage
  • Oligodeoxyribonucleotides / pharmacology*
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer


  • Adjuvants, Immunologic
  • Antibiotics, Antineoplastic
  • CPG-oligonucleotide
  • Delayed-Action Preparations
  • Oligodeoxyribonucleotides
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Doxorubicin