846
Evaluation of the adjuvant effect of gold nanocages
in vitro
Yavuz,E.
1,2
,Sakalak,H.
3
,Cavusoglu,H.
1,3
,Uyar,P.
1,4
,Yavuz,M.S.
1,3
,
Bagriacik,E.U.
2
1
SelcukUniversity,AdvancedTechnologyResearchandApplication
Center,Konya,Turkey,
2
GaziUniversityMedicalSchool, Immunology,
Ankara, Turkey,
3
SelcukUniversity,MetallurgyandMaterials Science
Engineering, Konya, Turkey,
4
Selcuk University,Biotechnology,Konya,
Turkey
Hepatitis B is a potentially life-threatening disease caused by
the hepatitis B virus (HBV). Unfortunately, despite the ongoing
vaccine campaigns HBV infection is not completely managed. In
order to increase the immune modulation capacities of Hepatitis B
vaccines different adjuvant systems have been studied. Especially
nanoparticle-based adjuvants are being widely investigated.
Biocompatible and bioinert gold nanoparticles have been
commonly used
invitro
and
invivo
biological research. Recently, gold
nanocages (AuNCs), a special designwith ultra thin porous walls and
hollow interiors, have shown ample potential and have a promising
future in the fields of cancer diagnostics and treatment. Our goal is to
use AuNCs as an adjuvant in Hepatitis Bmodel in vitro.
In this project, synthesized and characterized Au nanocages are
used.FollowingtheadsorptionofHBsAgproteinontoAu nanocages,
adsorption efficiency of AuNCs is investigated. The uptake of
HBsAg-AuNC by macrophages and its colocalization within the
cell are analyzed by flow cytometry and confocal microscopy. The
in vitro
effect of the internalization of only AuNCs or HBsAg-AuNC
on macrophage activation, antigen presentation and the cytokine
profile are analyzed by flow cytometry and ELISA techniques. Here
we aim to study the immunomodulation properties of the porous
goldnanoparticles as an adjuvant in vitro.
IL-15 activated NK cells overcame DC maturation defects
induced by head and neck cancer microenvironment
Upreti,D.,Zhang,M.,Kung,S.K.P.
UniversityofManitoba,Winnipeg,Canada
Head and neck squamous cell carcinoma (HNSCC) patients have the
lowest 5-year disease-free survival rate. There is need to develop
novel therapeutics of HNSCC. Natural Killer (NK) cells play key
roles in innate immunity against infections and transformed cells.
Through interactions with dendritic cell (DC), NK cells can shape also
subsequently induced adaptiveT-cell immunity.
Here we used an immunocompetent mouse model (AT-84) to
evaluate anti-tumor potential of IL-15 activated NK cells. A direct
injection of NK cells at tumor site significantly suppressed AT-84
tumor growth in vivo. It induced also protective memory responses
against a secondary AT-84 challenge. AT-84 tumor cell was relatively
resistant to IL-15 activated NK cells killing in vitro, suggesting that
direct killing of AT-84 is unlikely the major underlying mechanism.
We therefore hypothesized that IL-15 activated NK cells promoted
anti-tumor activities via NK-DC crosstalk. Using bone marrow
derived DC cultures; we observed that conditioned medium of
AT-84 impaired DC maturation induced by TLR ligands in vitro.
These DC were impaired in inducing T cell activations in vitro.
Addition of IL-15 NK cells to the AT-84-exposed DC overcame the
DC maturation and functional defects in vitro. These in vitro data
was further corroborated by in vivo data obtained from the tumor
infiltrating dendritic cells. Collectively, our data demonstrated that
IL-15 activated NK cells were able to reverse the immunosuppressed
DCs to an immunostimulatory state that correlated well with tumor
regressions. It supported future development of IL-15 NK-based
immunotherapy of HNSCC.
Plasticity in CD1d-lipid antigen recognition by non-canonical
NKT cells
Almeida,C.F.
1,2
,Sundararaj,S.
3,4
,LeNours,J.
3,4
,Patel,O.
3
,Cao,B.
5
,Pellicci,
D.G.
1,2
,Williams,S.
5
,Rossjohn,J.
3,4,6
,Uldrich, A.P.
1,2
,Godfrey,D.I.
1,2
1
The University of Melbourne and The Peter Doherty Institute
for Infection and Immunity, Department of Microbiology and
Immunology, Melbourne, Australia,
2
AustralianResearchCouncil
Centre of Excellence inAdvancedMolecular Imaging, The University
ofMelbourne,Melbourne,Australia,
3
SchoolofBiomedicalSciences,
MonashUniversity,DepartmentofBiochemistry andMolecular
Biology,Melbourne,Australia,
4
AustralianResearchCouncilCentre
ofExcellenceinAdvancedMolecularImaging, MonashUniversity,
Monash,Australia,
5
SchoolofChemistry,Bio21MolecularScienceand
BiotechnologyInstitute,TheUniversity ofMelbourne, Melbourne,
Australia,
6
Institute of Infectionand Immunity, CardiffUniversity,
School ofMedicineI, HeathPark, Cardiff,UnitedKingdom
Natural Killer T (NKT) cells are specialised lymphocytes that
recognise lipid antigens presented by the MHC Class I-like
molecule CD1d. Following activation, they rapidly secrete a broad
range of immunoregulatory cytokines that can influence other
mediators of immune responses and therefore they represent a
promising therapeutic target for cancer and other diseases. The
most extensively studied are type 1 NKT cells, which recognise a
derivative of a marine sponge glycolipid α-galactosylceramide
(α- GalCer), express a semi-invariant T cell receptor (TCR) and have
a well-established role in the immune system. Much less is known
about type 2 NKT cells, which do not recognise α-GalCer and express
a diverse TCR repertoire. Using a panel of CD1d mutants, we reveal
that different type 2 NKT cell hybridomas can adopt multipleways to
interact with CD1d, and furthermore, we identify a new population
of type 2 NKT cells that specifically recognises the microbial
derived lipid-antigen α-glucuronosyl- diacylglycerol (α-GlcA-
DAG). Single cell sequencing of CD1d-α-GlcA-DAG tetramer
+
cells
reveals a polyclonal TCR repertoire distinct from type 1 NKT cells.
Collectively, our results suggest that type 2 NKT cells express highly
diverse TCRs and rely on mechanisms different to type 1 NKT cells
to recognise distinct antigens. The knowledge obtained from these
studies increases the scope of antigens recognized by NKT cells and
provides valuable insight in how these cells can be manipulated for
therapeutic purposes.
Mucosal route of immunotherapy with transgenic rice seeds
expressing hypoallergenic whole T cell epitopes of Cryj1 and
Cryj2 - Investigation in murine model of cedar pollinosis
Kawauchi, H.
1
, Aoi, N.
1
, Yamada, T.
2
, Takagi, H.
3
, Takaiwa, F.
3
1
Shimane University, Faculty of Medicine, Otorhinolaryngology, Izumo,
Japan,
2
Shimane University, Center for Integrated Research in Science,
Department of Experimental Animals, Izumo, Japan,
3
National Institute
of Agrobiological Sciences, Ministry of Agriculture, Tsukuba, Japan
For the last decade, we have been investigating the therapeutic