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Budapest, Hungary

Kolonics A.,Hungarian Academy of Sciences | Kolonics A.,R and D Ultrafast Lasers Ltd | Csiszovszki Z.,Genetic Immunity Kft | Csiszovszki Z.,EMMUNITY Inc. | And 8 more authors.
Experimental Dermatology | Year: 2014

Epidermal Langerhans cells (LCs) function as professional antigen-presenting cells of the skin. We investigated the LC-targeting properties of a special mannose-moiety-coated pathogen-like synthetic nanomedicine DermaVir (DV), which is capable to express antigens to induce immune responses and kill HIV-infected cells. Our aim was to use multiphoton laser microscopy (MLM) in vivo in order to visualize the uptake of Alexa-labelled DV (AF546-DV) by LCs. Knock-in mice expressing enhanced green fluorescent protein (eGFP) under the control of the langerin gene (CD207) were used to visualize LCs. After 1 h, AF546-DV penetrated the epidermis and entered the eGFP-LCs. The AF546-DV signal was equally distributed inside the LCs. After 9 h, we observed AF546-DV signal accumulation that occurred mainly at the cell body. We demonstrated in live animals that LCs picked up and accumulated the nanoparticles in the cell body. © 2014 John Wiley & Sons A/S.

Toke E.R.,Genetic Immunity Kft | Toke E.R.,EMMUNITY Inc. | Lorincz O.,Genetic Immunity Kft | Lorincz O.,EMMUNITY Inc. | And 25 more authors.
Gene Therapy | Year: 2014

There is no clinically available cancer immunotherapy that exploits Langerhans cells (LCs), the epidermal precursors of dendritic cells (DCs) that are the natural agent of antigen delivery. We developed a DNA formulation with a polymer and obtained synthetic 'pathogen-like' nanoparticles that preferentially targeted LCs in epidermal cultures. These nanoparticles applied topically under a patch-elicited robust immune responses in human subjects. To demonstrate the mechanism of action of this novel vaccination strategy in live animals, we assembled a high-resolution two-photon laser scanning-microscope. Nanoparticles applied on the native skin poorly penetrated and poorly induced LC motility. The combination of nanoparticle administration and skin treatment was essential both for efficient loading the vaccine into the epidermis and for potent activation of the LCs to migrate into the lymph nodes. LCs in the epidermis picked up nanoparticles and accumulated them in the nuclear region demonstrating an effective nuclear DNA delivery in vivo. Tissue distribution studies revealed that the majority of the DNA was targeted to the lymph nodes. Preclinical toxicity of the LC-targeting DNA vaccine was limited to mild and transient local erythema caused by the skin treatment. This novel, clinically proven LC-targeting DNA vaccine platform technology broadens the options on DC-targeting vaccines to generate therapeutic immunity against cancer. © 2014 Macmillan Publishers Limited.

Csati D.,Hungarian Academy of Sciences | Szipocs R.,Hungarian Academy of Sciences | Szipocs R.,R and D Ultrafast Lasers Ltd
Fiber Lasers and Applications, FILAS 2012 | Year: 2012

Mode-locked operation of an all-fiber, all-normal dispersion Yb-fiber ring laser is actively optimized by a two-channel polarization controller according to the measured, normalised, single-sideband noise power. © 2012 OSA.

Kolonics A.,Hungarian Academy of Sciences | Kolonics A.,R and D Ultrafast Lasers Ltd | Csiszovszki Z.,Genetic Immunity | Toke E.,R and D Ultrafast Lasers Ltd | And 7 more authors.
Optical Molecular Probes, Imaging and Drug Delivery, OMP 2013 | Year: 2013

Fluorescently labelled polyethylenimine-mannose/DNA nanoparticles caused morphological and intracellular changes in Langerhans cells as studied by multiphoton laser microscopy in vivo in ear of knock-in mice expressing enhanced Green Fluorescent Protein under control of langerin gene. ©2013 The Optical Society (OSA).

Csati A.,Hungarian Academy of Sciences | Antal P.,Hungarian Academy of Sciences | Szipics R.,Hungarian Academy of Sciences | Szipics R.,R and D Ultrafast Lasers Ltd
Advances in Optical Materials, AIOM 2012 | Year: 2012

An inherently synchronized Yb-fiber laser based extension unit for femtosecond pulse, broadly tunable Ti-sapphire lasers is introduced, which is well suited for coherent anti-Stokes Raman scattering microscopy. © 2012 OSA.

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