Vaccination with poly-L-arginine as immunostimulant for peptide vaccines: induction of potent and long-lasting T-cell responses against cancer antigens.

نویسندگان

  • Frank Mattner
  • Julia-Kristina Fleitmann
  • Karen Lingnau
  • Walter Schmidt
  • Alena Egyed
  • Jörg Fritz
  • Wolfgang Zauner
  • Barbara Wittmann
  • Irmina Gorny
  • Manfred Berger
  • Helen Kirlappos
  • Aleksandr Otava
  • Max L Birnstiel
  • Michael Buschle
چکیده

Vaccines that induce high numbers of sustained T cell responses are urgently needed for the treatment of numerous diseases including cancer. Antigen-presenting cells (APCs), the most important of which are dendritic cells, orchestrate antigen-dependent T cell responses in that they present antigens to T cells in an appropriate environment. Here we present evidence that after vaccination with a simple mixture of the cationic poly-amino acid poly-L-arginine and tumor antigen-derived peptide antigens, large numbers of antigen-specific T cells are induced and APCs mediate the generation of T lymphocytes. We observe that after s.c. injection, MHC class II(+) cells infiltrate injection sites and are loaded with large amounts of antigen in vivo under the influence of poly-L-arginine. Consequently, numerous antigen-charged APCs can be detected in draining lymph nodes of vaccinated animals. Antigen-specific T cell responses induced are systemic and were readily detected more than 4 months after the last vaccination, the latest time point we measured. By contrast, even after repeat injections, we were consistently unable to detect antibody responses against poly-L-arginine, allowing this compound to be used for numerous booster injections. Clinical trials in cancer patients using poly-L-arginine as immunostimulant will be carried out in the near future.

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عنوان ژورنال:
  • Cancer research

دوره 62 5  شماره 

صفحات  -

تاریخ انتشار 2002