Chromogranin A as potential target for immunotherapy of malignant pheochromocytoma.
Currently, no effective treatment for malignant pheochromocytoma exists. The aim of our study was to investigate the role of chromogranin A (CgA) as a specific target molecule for immunotherapy in a murine model for pheochromocytoma. Six amino acid-modified and non-modified CgA peptides were used for dendritic cell vaccination. Altogether, 50 mice received two different CgA vaccination protocols; another 20 animals served as controls. In vitro tetramer analyses revealed large increases of CgA-specific cytotoxic T cells (CTL) in CgA-treated mice. Tumors of exogenous applied pheochromocytoma cells showed an extensive infiltration by CD8+ T cells. In vitro, CTL of CgA-treated mice exhibited strong MHC I restricted lysis capacities towards pheochromocytoma cells. Importantly, these mice showed strongly diminished outgrowth of liver tumors of applied pheochromocytoma cells. Our data clearly demonstrate that CgA peptide-based immunotherapy induces a cytotoxic immune response in experimental pheochromocytoma, indicating potential for therapeutic applications in patients with malignant pheochromocytoma.
Papewalis
Claudia
C
Department of Endocrinology, Diabetes and Rheumatology, University Hospital Duesseldorf, Germany. claudia.papewalis@uni-duesseldorf.de
Kouatchoua
Christiane
C
Ehlers
Margret
M
Jacobs
Benedikt
B
Porwol
Dominika
D
Schinner
Sven
S
Willenberg
Holger S
HS
Anlauf
Martin
M
Raffel
Andreas
A
Eisenhofer
Graeme
G
Neumann
Hartmut P H
HP
Bornstein
Stefan R
SR
Scherbaum
Werner A
WA
Schott
Matthias
M
D000310:Adrenal Gland Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000595:Amino Acid Sequence; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D053379:Chromogranin A / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology*; D010673:Pheochromocytoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D019496:Cancer Vaccines; D053379:Chromogranin A; D010455:Peptides