BRAF peptide vaccine facilitates therapy of murine BRAF-mutant melanoma

Abstract

Approximately, 50% of human melanomas are driven by BRAF mutations, which produce tumors that are highly immunosuppressive and often resistant to vaccine therapy. We introduced lipid-coated calcium phosphate nanoparticles (LCP NPs) as a carrier to efficiently deliver a tumor-specific antigen, the BRAFV600E peptide, to drive dendritic cell (DC) maturation and antigen presentation in C57BL6 mice. The BRAF peptide vaccine elicited a robust, antigen-specific cytotoxic T cell response and potent tumor growth inhibition in a murine BRAF-mutant melanoma model. Advanced BRAF-specific immune response was illustrated by IFN-γ production assay and cytotoxic T lymphocyte (CTL) assay. Remodeling of immunosuppressive modules within the tumor microenvironment further facilitated CTL infiltration. Thus, using LCP NPs to deliver the BRAF peptide vaccine is a promising strategy for the BRAF-mutant melanoma therapy.

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Abbreviations

CCL2:

C-C Motif chemokine 2

CFSE:

Carboxyfluorescein succinimidyl ester

DOPA:

Dioleoylphosphatydic acid

DOTAP:

(±)-N,N,N-Trimethyl-2,3-bis(z-octadec-9-ene-oyloxy)-1-propanaminium chloride

DSPE-PEG-2000:

1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000

DSPE-PEG-NHS:

3-(N-succinimidyloxyglutaryl) aminopropyl, polyethyleneglycol-carbamyl-distearoylphosphatidylethanolamine

FAP:

Fibroblast activation protein

LCP NP:

Lipid-coated calcium phosphate nanoparticle

ODN:

Oligodeoxynucleotides

OS:

Overall survival

TEM:

Transmission electron microscope

Th1:

Type 1 T helper

TME:

Tumor microenvironment

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Acknowledgements

The work was supported by NIH Grants CA149387 and CA198999. Leaf Huang is a Senior Visiting Scholar of the State Key Laboratory of Molecular Engineering of Polymers, Fudan University, China.

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Correspondence to Leaf Huang.

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Cite this article

Liu, Q., Zhu, H., Liu, Y. et al. BRAF peptide vaccine facilitates therapy of murine BRAF-mutant melanoma. Cancer Immunol Immunother 67, 299–310 (2018). https://doi.org/10.1007/s00262-017-2079-7

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Keywords

  • BRAF-mutant melanoma
  • Peptide vaccine
  • Immunotherapy
  • Nanoparticles