Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators

Nat Nanotechnol. 2019 Sep;14(9):891-901. doi: 10.1038/s41565-019-0512-0. Epub 2019 Aug 5.


A low response rate, acquired resistance and severe side effects have limited the clinical outcomes of immune checkpoint therapy. Here, we show that combining cancer nanovaccines with an anti-PD-1 antibody (αPD-1) for immunosuppression blockade and an anti-OX40 antibody (αOX40) for effector T-cell stimulation, expansion and survival can potentiate the efficacy of melanoma therapy. Prophylactic and therapeutic combination regimens of dendritic cell-targeted mannosylated nanovaccines with αPD-1/αOX40 demonstrate a synergism that stimulates T-cell infiltration into tumours at early treatment stages. However, this treatment at the therapeutic regimen does not result in an enhanced inhibition of tumour growth compared to αPD-1/αOX40 alone and is accompanied by an increased infiltration of myeloid-derived suppressor cells in tumours. Combining the double therapy with ibrutinib, a myeloid-derived suppressor cell inhibitor, leads to a remarkable tumour remission and prolonged survival in melanoma-bearing mice. The synergy between the mannosylated nanovaccines, ibrutinib and αPD-1/αOX40 provides essential insights to devise alternative regimens to improve the efficacy of immune checkpoint modulators in solid tumours by regulating the endogenous immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / therapeutic use
  • Drug Carriers / chemistry*
  • Immunization
  • Male
  • Mannose / chemistry*
  • Melanoma / immunology
  • Melanoma / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Tumor Microenvironment


  • Antibodies, Monoclonal
  • Cancer Vaccines
  • Drug Carriers
  • Mannose