Prostate stem cell antigen is a putative target for immunotherapy in pancreatic cancer.
The prostate stem cell antigen (PSCA) is a glycosylphosphatidyl-inositol (GPI)-linked cell surface antigen expressed in normal prostate and overexpressed in the majority of prostate cancers and correlates with tumor grade and disease stage. Because PSCA has been described to be up-regulated in pancreatic cancer, the purpose was to evaluate the expression of PSCA in human pancreatic cancer. Furthermore, the therapeutic efficacy of a monoclonal anti-PSCA antibody in an in vivo pancreatic cancer model was determined.


METHODS
The expression of PSCA in human pancreatic cancer tissues was determined and compared with chronic pancreatitis and normal pancreas by quantitative reverse transcriptase-polymerase chain reaction. Therapeutic efficacy of the monoclonal anti-PSCA antibody 1G8 was examined in Capan-1 pancreatic tumors grown as subcutaneous grafts in athymic nude mice.


RESULTS
PSCA was strongly up-regulated in human pancreatic cancer compared with chronic pancreatitis and normal pancreas. In addition, the PSCA protein was expressed on the cell surface of pancreatic cancer cells. Treatment with 1G8 significantly reduced tumor growth initiation in an in vivo pancreatic cancer xenograft model. In addition, antibody treatment of established tumors reduced tumor progression.


CONCLUSIONS
These results show a potential therapeutic role for anti-PSCA antibodies in the treatment of pancreatic cancer. Furthermore, PSCA might serve as a novel marker in the diagnosis of pancreatic cancer.
Wente
Moritz N
MN
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Jain
Anjali
A
Kono
Evelyn
E
Berberat
Pascal O
PO
Giese
Thomas
T
Reber
Howard A
HA
Friess
Helmut
H
Büchler
Markus W
MW
Reiter
Robert E
RE
Hines
Oscar J
OJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D051936:Centromere Protein B; D005260:Female; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010179:Pancreas / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D050500:Pancreatitis, Chronic / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D051936:Centromere Protein B; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D012333:RNA, Messenger