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

• Published in: Cancer research (Chicago, Ill.) Ill.), 2002-03, Vol.62 (5), p.1477-1480
• Main Authors: MATTNER, Frank, FLEITMANN, Julia-Kristina, KIRLAPPOS, Helen, OTAVA, Aleksandr, BIRNSTIEL, Max L, BUSCHLE, Michael, LINGNAU, Karen, SCHMIDT, Walter, EGYED, Alena, FRITZ, Jörg, ZAUNER, Wolfgang, WITTMANN, Barbara, GORNY, Irmina, BERGER, Manfred
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antigen-Presenting Cells - drug effects; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - physiology; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; Cancer Vaccines - immunology; Cell Movement - drug effects; Female; Histocompatibility Antigens Class II - analysis; Immunotherapy; Intramolecular Oxidoreductases - immunology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Peptides - pharmacology; Pharmacology. Drug treatments; T-Lymphocytes - immunology; Vaccination
• ISSN: 0008-5472; 1538-7445

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.