title: Potentiating Cancer Immunotherapy Using Papaya Mosaic Virus-Derived Nanoparticles.
abstract: The recent development of novel immunotherapies is revolutionizing cancer treatment. These include, for example, immune checkpoint blockade, immunomodulation, or therapeutic vaccination. Although effective on their own, combining multiple approaches will most likely be required in order to achieve the maximal therapeutic benefit. In this regard, the papaya mosaic virus nanoparticle (PapMV) has shown tremendous potential as (i) an immunostimulatory molecule, (ii) an adjuvant, and (iii) a vaccine platform through its intrinsic capacity to activate the innate immune response in an IFN-α-dependent manner. Here, we demonstrate that intratumor administration of PapMV significantly slows down melanoma progression and prolongs survival. This correlates with enhanced chemokine and pro-inflammatory-cytokine production in the tumor and increased immune-cell infiltration. Proportions of total and tumor-specific CD8(+) T cells dramatically increase following PapMV treatment whereas those of myeloid-derived suppressor cells (MDSC) concomitantly decrease. Moreover, systemic PapMV administration prevents metastatic tumor-implantation in the lungs. Importantly, PapMV also synergistically improves the therapeutic benefit of dendritic cell (DC)-based vaccination and PD-1 blockade by potentiating antitumor immune responses. This study illustrates the immunostimulatory potential of a plant virus-derived nanoparticle for cancer therapy either alone or in conjunction with other promising immunotherapies in clinical development.
authors.affiliation: Immunovirology Laboratory, Institut national de la recherche scientifique (INRS), INRS-Institut Armand-Frappier , Laval, Quebec Canada , H7V 1B7.
authors.forename: Marie-Ève
authors.initials: MÈ
authors.lastname: Lebel
authors.affiliation: Immunovirology Laboratory, Institut national de la recherche scientifique (INRS), INRS-Institut Armand-Frappier , Laval, Quebec Canada , H7V 1B7.
authors.forename: Karine
authors.initials: K
authors.lastname: Chartrand
authors.affiliation: Immunovirology Laboratory, Institut national de la recherche scientifique (INRS), INRS-Institut Armand-Frappier , Laval, Quebec Canada , H7V 1B7.
authors.forename: Esther
authors.initials: E
authors.lastname: Tarrab
authors.forename: Pierre
authors.initials: P
authors.lastname: Savard
authors.forename: Denis
authors.initials: D
authors.lastname: Leclerc
authors.affiliation: Immunovirology Laboratory, Institut national de la recherche scientifique (INRS), INRS-Institut Armand-Frappier , Laval, Quebec Canada , H7V 1B7.
authors.forename: Alain
authors.initials: A
authors.lastname: Lamarre
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D029441:Carica / Q000821:virology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology; D005260:Female; D007167:Immunotherapy; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D009029:Mosaic Viruses / Q000737:chemistry / Q000276:immunology*; D053758:Nanoparticles / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016207:Cytokines
keywords: Cancer immunotherapy; immune checkpoint blockade; immunomodulation; plant virus-derived nanoparticle; therapeutic vaccination