MORÓN VÍCTOR GABRIEL
Congresos y reuniones científicas
Título:
IDENTIFICATION OF ANTIGEN CROSS-PRESENTATION POTENTIATING DRUGS FOR VACCINE DEVELOPMENT
Autor/es:
MARÍA INÉS CRESPO; M LAURA GUANTAY; MERCEDES PASCUAL; NICOLAS DANIEL DHO; MARÍA C PISTORESI- PALENCIA; BELKYS A. MALETTO; GASTON SORIA; G MORON
Lugar:
virtual
Reunión:
Congreso; LXIX REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2021
Institución organizadora:
SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI)
Resumen:
The cytotoxic CD8 T cell (CTL) mediated-immune response is crucial
for tumor immunotherapy and for protective immunity against
intracellular pathogens. Dendritic cells (DC) have the ability to internalize
and present exogenous antigens (Ag) bound to MHC I to
activate naïve CD8 T cells through a process known as cross-presentation.
Subunit vaccines are often poorly immunogenic and adjuvants
are required to boost immunity. The complexity of antigen
cross-presentation pathways makes difficult to identify therapeutic
targets that can act as adjuvants able to generate protective CTL
responses. We performed a high throughput screening of libraries of
drugs approved by international agencies to identify compounds and
molecular pathways capable of enhancing Ag cross-presentation in
DCs. For it, we developed a high-performance screening method by
adapting the colorimetric B3Z presentation assay using JAWSII DC
cell line and Ovalbumin (OVA) as Ag. After assayed 1760 drugs, we
found 1.1% of them increased OVA cross-presentation. We validated
these hits and functional analogs by performing dose-response
assays with both JAWSII and GMCSF BMDCs. Almost all of hits are
lysosomotropic drugs that could promote biomacromolecules accumulation.
As lipid bodies (LB)-formation has been associated to DCs
cross-presentation ability, five hits were evaluated for LBs formation
in JAWSII cells by fluorescence microscopy. We found that Tolonium
Chloride, Amodiaquine Dihydrochloride and Perhexiline Maleate
increased the amount of LBs per cell. None of these five drugs produced
an important increase neither in the MHCI-surface expression
nor in the soluble OVA-endocytosis by JAWSII cells. In conclusion,
we established a sensitive, fast and robust screening platform for
compounds-search capable of stimulating Ag cross-presentation in
DCs. Although the mechanism of action of these drugs is still under
investigation, our preliminary results indicate that it is likely related
to lipid metabolism.
for tumor immunotherapy and for protective immunity against
intracellular pathogens. Dendritic cells (DC) have the ability to internalize
and present exogenous antigens (Ag) bound to MHC I to
activate naïve CD8 T cells through a process known as cross-presentation.
Subunit vaccines are often poorly immunogenic and adjuvants
are required to boost immunity. The complexity of antigen
cross-presentation pathways makes difficult to identify therapeutic
targets that can act as adjuvants able to generate protective CTL
responses. We performed a high throughput screening of libraries of
drugs approved by international agencies to identify compounds and
molecular pathways capable of enhancing Ag cross-presentation in
DCs. For it, we developed a high-performance screening method by
adapting the colorimetric B3Z presentation assay using JAWSII DC
cell line and Ovalbumin (OVA) as Ag. After assayed 1760 drugs, we
found 1.1% of them increased OVA cross-presentation. We validated
these hits and functional analogs by performing dose-response
assays with both JAWSII and GMCSF BMDCs. Almost all of hits are
lysosomotropic drugs that could promote biomacromolecules accumulation.
As lipid bodies (LB)-formation has been associated to DCs
cross-presentation ability, five hits were evaluated for LBs formation
in JAWSII cells by fluorescence microscopy. We found that Tolonium
Chloride, Amodiaquine Dihydrochloride and Perhexiline Maleate
increased the amount of LBs per cell. None of these five drugs produced
an important increase neither in the MHCI-surface expression
nor in the soluble OVA-endocytosis by JAWSII cells. In conclusion,
we established a sensitive, fast and robust screening platform for
compounds-search capable of stimulating Ag cross-presentation in
DCs. Although the mechanism of action of these drugs is still under
investigation, our preliminary results indicate that it is likely related
to lipid metabolism.
