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Vaccination with Poly-L-Arginine As Immunostimulant for Peptide Vaccines: Induction of Potent and Long-Lasting T-Cell Responses against Canc
Vaccination with Poly-L-Arginine As Immunostimulant for Peptide Vaccines: Induction of Potent and Long-Lasting T-Cell Responses against Cancer Antigens
Frank Mattner,1 Julia-Kristina Fleitmann,1 Karen Lingnau, Walter Schmidt, Alena Egyed, Jo¨ rg Fritz, Wolfgang Zauner, Barbara Wittmann, Irmina Gorny, Manfred Berger, Helen Kirlappos, Aleksandr Otava, Max L. Birnstiel, and Michael Buschle2
Intercell Biomedizinische Forschungs und Entwicklungs AG, Rennweg 95B, 1030 Vienna, Austria
[CANCER RESEARCH 62, 1477–1480, March 1, 2002]
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.