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

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

Publication date: Aug 05, 2019

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.

Conniot, J., Scomparin, A., Peres, C., Yeini, E., Pozzi, S., Matos, A.I., Kleiner, R., Moura, L.I.F., Zupancic, E., Viana, A.S., Doron, H., Gois, P.M.P., Erez, N., Jung, S., Satchi-Fainaro, R., and Florindo, H.F. Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators. 23652. 2019 Nat Nanotechnol.

Concepts Keywords
Antibody Melanoma therapy
Blockade Efficacy melanoma
Dendritic Cell Immunosuppression
Endogenous Immunization
Immune Response Medical specialties
Immunosuppression Medicine
Inhibitor Immune system
Melanoma Organ systems
Mice Immune checkpoint
Microenvironment CD134
Myeloid T cell
Remission Melanoma
Suppressor Tumor microenvironment
Synergism Cancer immunotherapy
Synergy
T Cell
Tumour

Semantics

Type Source Name
drug DRUGBANK Ibrutinib
disease MESH growth
gene UNIPROT RPL17
disease DOID cancer
disease MESH cancer
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma

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