Minimal residual disease in ovarian cancer as a target for complement-mediated mAb immunotherapy.
Ovarian cancer is potentially well suited for local monoclonal antibody (mAb) immunotherapy, because it remains within the peritoneal cavity for a long period of time before giving rise to distant metastases. At the stage of minimal residual disease, the cells appear to be in a state of dormancy (G(0)) or at least have lower rates of tumour cell proliferation. They should be a promising target for immunotherapy. Here we first examined the cell-cycle expression of CD59 and decay-accelerating factor (DAF; CD55) on four different ovarian carcinoma cell lines, using simultaneous flow cytometric analysis of DNA content or the cell-cycle-specific nuclear proliferation protein Ki67 and CD59 or DAF surface expression. We found that CD59 and DAF are stably expressed throughout the cell cycle. The polyvalent approach to target-independent antigens to improve the efficiency of mAb complement (C)-mediated damages was promising, and tumour cells become sensitive to C damage, when incubated with cross-linked mAb against different tumour-associated antigens. Although, such immune complex-mediated C activation was rather ineffective in killing the cells, it could be potentiated by the addition of blocking mAb against CD59 and DAF. Our results suggest that the activities of intrinsic C regulators must be neutralized to make minimal residual disease a promising target for antibody therapy.
Bjørge
L
L
Department of Obstetrics and Gynecology, Institute of Clinical Medicine, Haukeland University Hospital, Bergen, Norway. line.bjorge@gades.uib.no
Stoiber
H
H
Dierich
M P
MP
Meri
S
S
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology; D019138:Antibodies, Blocking / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000032:analysis; D018958:CD55 Antigens / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D003165:Complement System Proteins / Q000276:immunology*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy; D019394:Ki-67 Antigen / Q000032:analysis / Q000378:metabolism; D018365:Neoplasm, Residual; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D018958:CD55 Antigens; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D003165:Complement System Proteins