title: Recombinant Lactobacillus plantarum induces immune responses to cancer testis antigen NY-ESO-1 and maturation of dendritic cells.
abstract: Given their safe use in humans and inherent adjuvanticity, Lactic Acid Bacteria may offer several advantages over other mucosal delivery strategies for cancer vaccines. The objective of this study is to evaluate the immune responses in mice after oral immunization with Lactobacillus (L) plantarum WCFS1 expressing a cell-wall anchored tumor antigen NY-ESO-1. And to investigate the immunostimulatory potency of this new candidate vaccine on human dendritic cells (DCs). L. plantarum displaying NY-ESO-1 induced NY-ESO-1 specific antibodies and T-cell responses in mice. By contrast, L. plantarum displaying conserved proteins such as heat shock protein-27 and galectin-1, did not induce immunity, suggesting that immune tolerance to self-proteins cannot be broken by oral administration of L. plantarum. With respect to immunomodulation, immature DCs incubated with wild type or L. plantarum-NY-ESO-1 upregulated the expression of co-stimulatory molecules and secreted a large amount of interleukin (IL)-12, TNF-α, but not IL-4. Moreover, they upregulated the expression of immunosuppressive factors such as IL-10 and indoleamine 2,3-dioxygenase. Although L. plantarum-matured DCs expressed inhibitory molecules, they stimulated allogeneic T cells in-vitro. Collectively, the data indicate that L. plantarum-NY-ESO-1 can evoke antigen-specific immunity upon oral administration and induce DC maturation, raising the potential of its use in cancer immunotherapies.
authors.affiliation: a Department of Cancer Immunology ; Institute for Cancer Research; Oslo University Hospital ; Oslo , Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Mobergslien
authors.affiliation: b Department of Pathology ; Oslo University Hospital ; Oslo , Norway.
authors.forename: Vlada
authors.initials: V
authors.lastname: Vasovic
authors.affiliation: c Department of Chemistry ; Biotechnology and Food Science; Norwegian University of Life Sciences (NMBU) ; Ås , Norway.
authors.forename: Geir
authors.initials: G
authors.lastname: Mathiesen
authors.affiliation: c Department of Chemistry ; Biotechnology and Food Science; Norwegian University of Life Sciences (NMBU) ; Ås , Norway.
authors.forename: Lasse
authors.initials: L
authors.lastname: Fredriksen
authors.affiliation: a Department of Cancer Immunology ; Institute for Cancer Research; Oslo University Hospital ; Oslo , Norway.
authors.forename: Phuong
authors.initials: P
authors.lastname: Westby
authors.affiliation: c Department of Chemistry ; Biotechnology and Food Science; Norwegian University of Life Sciences (NMBU) ; Ås , Norway.
authors.forename: Vincent G H
authors.initials: VG
authors.lastname: Eijsink
authors.affiliation: b Department of Pathology ; Oslo University Hospital ; Oslo , Norway.
authors.forename: Qian
authors.initials: Q
authors.lastname: Peng
authors.affiliation: a Department of Cancer Immunology ; Institute for Cancer Research; Oslo University Hospital ; Oslo , Norway.
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D004337:Drug Carriers / Q000378:metabolism*; D005260:Female; D048191:Lactiplantibacillus plantarum / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015854:Up-Regulation; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D016207:Cytokines; D004337:Drug Carriers; D008565:Membrane Proteins; D014614:Vaccines, Synthetic
keywords: Lactobacillus plantarum; adjuvants; dendritic cells; oral immunization; tumor antigens