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

Abstract

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.

• Authors: 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
• Journal: Cancer research (Cancer Res) Vol. 62 Issue 5 Pg. 1477-80 (Mar 01 2002) ISSN: 0008-5472 [Print] United States
• PMID: 11888923 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• Cancer Vaccines
• Histocompatibility Antigens Class II
• Peptides
• polyarginine
• Intramolecular Oxidoreductases
• dopachrome isomerase

Topics

• Adjuvants, Immunologic (pharmacology)
• Animals
• Antigen-Presenting Cells (drug effects, immunology, physiology)
• Antigens, Neoplasm (immunology)
• Cancer Vaccines (immunology)
• Cell Movement (drug effects)
• Female
• Histocompatibility Antigens Class II (analysis)
• Intramolecular Oxidoreductases (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Peptides (pharmacology)
• T-Lymphocytes (immunology)
• Vaccination