Previous Page  816 / 827 Next Page
Information
Show Menu
Previous Page 816 / 827 Next Page
Page Background

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