Vaccination with poly-L-arginine as immunostimulant for peptide vaccines: induction of potent and long-lasting T-cell responses against cancer antigens.
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.
Mattner
Frank
F
Intercell Biomedizinische Forschungs und Entwicklungs AG, Rennweg 95B, 1030 Vienna, Austria.
Fleitmann
Julia-Kristina
JK
Lingnau
Karen
K
Schmidt
Walter
W
Egyed
Alena
A
Fritz
Jörg
J
Zauner
Wolfgang
W
Wittmann
Barbara
B
Gorny
Irmina
I
Berger
Manfred
M
Kirlappos
Helen
H
Otava
Aleksandr
A
Birnstiel
Max L
ML
Buschle
Michael
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D019746:Intramolecular Oxidoreductases / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010455:Peptides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C015462:polyarginine; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase