In vivo induction of dendritic cell-mediated cytotoxicity against allogeneic pancreatic carcinoma cells.
The objective of this study was to assess the toxicity and immunological response induced by autologous dendritic cells (DCs) pulsed with allogeneic tumor lysate in a pancreatic cancer patient. The lack of available tumor peptides in pancreatic cancer strongly supports the idea to use allogeneic tumor cells as a source of antigens. The patient suffering from a stage IV pancreatic cancer received 1-2x10(7) autologous monocyte-derived DCs in three-week intervals injected into a groin lymph node. Monocytes from peripheral blood were isolated by magnetic bead selection. For the first ten vaccinations DCs were loaded with autologous tumor cell lysate obtained during surgical exploration. After consumption of the autologous lysate, equal numbers of DCs were pulsed with lysate of the tumor cell line AsPc-1 and BxPc-3 for a further five vaccinations. Peripheral mononuclear cells (PMNCs) were harvested after the seventh and compared with PMNCs obtained after the fourteenth vaccination for immunological response. Delayed type hypersensitivity reactivity to DCs pulsed with autologous and allogeneic tumor lysate was also assessed. The patient received a total of fifteen vaccinations. There was no toxicity or evidence of autoimmunity observed. Delayed type hypersensitivity was found to be positive for the autologous as well as the allogeneic tumor lysate pulsed DCs. in vitro cytotoxicity assays demonstrated a dramatic increase of the PMNC killing capacity against the pancreatic cancer cell lines AsPc-1 and BxPc-3 after the fourteenth compared to the seventh vaccination. CT scans revealed a stable disease for six months. The administration of autologous DCs pulsed with allogeneic tumor lysate is non-toxic and suitable for inducing an immunological anti-tumor response. Even though this study was confined to a single patient, the data might open a door for novel immunotherapeutical strategies.
Stift
Anton
A
Department of Surgery, University of Vienna Medical School, A-1090 Vienna, Austria. a.stift@akh-wien.ac.at
Friedl
Josef
J
Dubsky
Peter
P
Bachleitner-Hofmann
Thomas
T
Benkoe
Thomas
T
Brostjan
Christine
C
Jakesz
Raimund
R
Gnant
Michael
M
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D017809:Fatal Outcome; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D016130:Immunophenotyping; D007167:Immunotherapy; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014057:Tomography, X-Ray Computed; D014182:Transplantation, Autologous; D014611:Vaccination
D000951:Antigens, Neoplasm; D001324:Autoantigens; D019496:Cancer Vaccines; D007519:Isoantigens