INVESTIGADORES
FAINBOIM Leonardo
artículos
Título:
Innate-immunity cytokines induced by VSSP, a Neisseria-derived immunological adjuvant
Autor/es:
VENIER C, GUTHMANN M, FERNANDEZ L, FAINBOIM L.
Revista:
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2007 vol. 147 p. 379 - 388
ISSN:
0009-9104
Resumen:
<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:595.3pt 841.9pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Neisserial outermembrane proteins have been combined with monosialoganglioside GM3 to formvery small size proteoliposomes (VSSP), a nanoparticulated formulation used as a cancer vaccine for the treatment of cancer patients with GM3-positive tumours. VSSP were shown to elicit anti-GM3 and antitumour immune responses. VSSP have also been shown to be an efficient adjuvant for tumour-cell and peptide-antigen vaccines in mice. In vitro studies showed that VSSP promote maturation of both murine and human dendritic cells, suggesting that VSSP could be used as efficient adjuvants. In order to study further the capacity of VSSP to elicit innate immune responses, human peripheral blood mononuclear cells and monocytes derived thereof were assessed for in vitro secretion of interleukin (IL)-10, IL-6, IL-12 and interferon (IFN)-g. VSSP most prominently induced the secretion of IL-6. IL-10 was secreted at a lower level. IL-12 p40 (but no p70) was also detected. IFN-g response was observed in 56% of the tested samples.Cytokine secretion was not related to lipopolysaccharide (LPS) content and involved Toll-like receptor 2 (TLR2)-mediated signal transduction. VSSP also induced DC maturation and a cytokine secretion pattern (high IL-6/low IL-10) which differs from that induced by LPS. The observed proinflammatory cytokine secretion pattern and the capacity of VSSP to drive DC maturation are examined in the light of the properties of other bacterial derivatives currently being user for immunotherapy purposes. Our results suggest that VSSP could be tested in clinical settings where T helper 1-type immune responses would be beneficial.