Tumor-targeted delivery of sunitinib base enhances vaccine therapy for advanced melanoma by remodeling the tumor microenvironment

Meirong Huo, Yan Zhao, Andrew Benson Satterlee, Yuhua Wang, Ying Xu, Leaf Huang

Research output: Research - peer-reviewArticle

  • 5 Citations

Abstract

Development of an effective treatment against advanced tumors remains a major challenge for cancer immunotherapy. We have previously developed a potent mannose-modified lipid calcium phosphate (LCP) nanoparticle (NP)-based Trp2 vaccine for melanoma therapy, but because this vaccine can induce a potent anti-tumor immune response only during the early stages of melanoma, poor tumor growth inhibition has been observed in more advanced melanoma models, likely due to the development of an immune-suppressive tumor microenvironment (TME). To effectively treat this aggressive tumor, a multi-target receptor tyrosine kinase inhibitor, sunitinib base, was efficiently encapsulated into a targeted polymeric micelle nano-delivery system (SUNb-PM), working in a synergistic manner with vaccine therapy in an advanced mouse melanoma model. SUNb-PM not only increased cytotoxic T-cell infiltration and decreased the number and percentage of MDSCs and Tregs in the TME, but also induced a shift in cytokine expression from Th2 to Th1 type while remodeling the tumor-associated fibroblasts, collagen, and blood vessels in the tumor. Additionally, inhibition of the Stat3 and AKT signaling pathways by SUNb-PM may induce tumor cell apoptosis or decrease tumor immune evasion. Our findings indicated that targeted delivery of a tyrosine kinase inhibitor to tumors can be used in a novel synergistic way to enhance the therapeutic efficacy of existing immune-based therapies for advanced melanoma.

LanguageEnglish (US)
Pages81-94
Number of pages14
JournalJournal of Controlled Release
Volume245
DOIs
StatePublished - Jan 10 2017

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Active Immunotherapy
Tumor Microenvironment
Melanoma
Neoplasms
sunitinib
Therapeutics
Vascular Tissue Neoplasms
Tumor Escape
Receptor Protein-Tyrosine Kinases
Micelles
Mannose
Protein-Tyrosine Kinases
Immunotherapy
Nanoparticles
Collagen
Vaccines
Apoptosis
Cytokines
T-Lymphocytes
Lipids

Keywords

  • Advanced melanoma
  • Peptide vaccine
  • Polymeric micelles
  • Sunitinib base
  • Tumor microenvironment

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Tumor-targeted delivery of sunitinib base enhances vaccine therapy for advanced melanoma by remodeling the tumor microenvironment. / Huo, Meirong; Zhao, Yan; Satterlee, Andrew Benson; Wang, Yuhua; Xu, Ying; Huang, Leaf.

In: Journal of Controlled Release, Vol. 245, 10.01.2017, p. 81-94.

Research output: Research - peer-reviewArticle

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