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A long-lasting dendritic cell DNA vaccination system using lysinylated amphiphiles with mannose-mimicking head-groups.

Abstract
Dendritic cells (DCs) pulsed/transduced with tumor-associated or viral antigens have shown promise in combating cancer and infectious diseases. Despite significant progresses, development of a biologically safe DC-based genetic immunization (DNA vaccination) system capable of providing truly long-lasting protective immunity remains a significant scientific challenge. Here we show that immunization with autologous DCs pre-transfected with electrostatic complexes (lipoplexes) of a plasmid DNA encoding melanoma tumor associated antigen and liposomes of two lysinylated cationic amphiphiles with mannose-mimicking quinic and shikimic acid head-groups provides long-lasting (300 days post tumor challenge) protective immunity with significant memory response (more than six months after the second tumor challenge) in more than 80% immunized mice. The presently described non-viral ex vivo DC-transfection system may be exploited in inducing long-lasting immune response in DC-based genetic immunization.
AuthorsRamishetti Srinivas, Arup Garu, Gopikrishna Moku, Sachin B Agawane, Arabinda Chaudhuri
JournalBiomaterials (Biomaterials) Vol. 33 Issue 26 Pg. 6220-9 (Sep 2012) ISSN: 1878-5905 [Electronic] Netherlands
PMID22658799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Ltd. All rights reserved.
Chemical References
  • Vaccines, DNA
  • Interleukin-4
  • Interferon-gamma
  • Mannose
Topics
  • Animals
  • Antigen-Presenting Cells (immunology, metabolism)
  • Cell Line, Tumor
  • Cells, Cultured
  • Dendritic Cells (immunology, metabolism)
  • Flow Cytometry
  • Interferon-gamma (metabolism)
  • Interleukin-4 (metabolism)
  • Male
  • Mannose (chemistry)
  • Melanoma (immunology, metabolism, prevention & control)
  • Mice
  • Mice, Inbred C57BL
  • Transfection (methods)
  • Vaccines, DNA (chemistry, therapeutic use)

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