Exploitation of Langerhans cells for in vivo DNA vaccine delivery into the lymph nodes

E. R. Toke, O. Lorincz, Z. Csiszovszki, E. Somogyi, G. Felföldi, L. Molnár, R. Szipócs, A. Kolonics, B. Malissen, F. Lori, J. Trocio, N. Bakare, F. Horkay, N. Romani, C. H. Tripp, P. Stoitzner, J. Lisziewicz

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)566-574
Number of pages9
JournalGene Therapy
Volume21
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

DNA Vaccines
Langerhans Cells
Lymph Nodes
Nanoparticles
Epidermis
Skin
DNA
Vaccines
Tissue Distribution
Erythema
Photons
Immunotherapy
Dendritic Cells
Cell Movement
Immunity
Neoplasms
Polymers
Vaccination
Lasers
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Medicine(all)

Cite this

Toke, E. R., Lorincz, O., Csiszovszki, Z., Somogyi, E., Felföldi, G., Molnár, L., ... Lisziewicz, J. (2014). Exploitation of Langerhans cells for in vivo DNA vaccine delivery into the lymph nodes. Gene Therapy, 21(6), 566-574. https://doi.org/10.1038/gt.2014.29

Exploitation of Langerhans cells for in vivo DNA vaccine delivery into the lymph nodes. / Toke, E. R.; Lorincz, O.; Csiszovszki, Z.; Somogyi, E.; Felföldi, G.; Molnár, L.; Szipócs, R.; Kolonics, A.; Malissen, B.; Lori, F.; Trocio, J.; Bakare, N.; Horkay, F.; Romani, N.; Tripp, C. H.; Stoitzner, P.; Lisziewicz, J.

In: Gene Therapy, Vol. 21, No. 6, 2014, p. 566-574.

Research output: Contribution to journalArticle

Toke, ER, Lorincz, O, Csiszovszki, Z, Somogyi, E, Felföldi, G, Molnár, L, Szipócs, R, Kolonics, A, Malissen, B, Lori, F, Trocio, J, Bakare, N, Horkay, F, Romani, N, Tripp, CH, Stoitzner, P & Lisziewicz, J 2014, 'Exploitation of Langerhans cells for in vivo DNA vaccine delivery into the lymph nodes', Gene Therapy, vol. 21, no. 6, pp. 566-574. https://doi.org/10.1038/gt.2014.29
Toke ER, Lorincz O, Csiszovszki Z, Somogyi E, Felföldi G, Molnár L et al. Exploitation of Langerhans cells for in vivo DNA vaccine delivery into the lymph nodes. Gene Therapy. 2014;21(6):566-574. https://doi.org/10.1038/gt.2014.29
Toke, E. R. ; Lorincz, O. ; Csiszovszki, Z. ; Somogyi, E. ; Felföldi, G. ; Molnár, L. ; Szipócs, R. ; Kolonics, A. ; Malissen, B. ; Lori, F. ; Trocio, J. ; Bakare, N. ; Horkay, F. ; Romani, N. ; Tripp, C. H. ; Stoitzner, P. ; Lisziewicz, J. / Exploitation of Langerhans cells for in vivo DNA vaccine delivery into the lymph nodes. In: Gene Therapy. 2014 ; Vol. 21, No. 6. pp. 566-574.
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