Immunotherapy of human ovarian carcinoma with OvaRex MAb-B43.13 in a human-PBL-SCID/BG mouse model.
The monoclonal antibody (MAb) B43.13, binding to the ovarian cancer-associated antigen CA125, has been injected into more than 200 patients with ovarian cancer to detect recurrence of the disease. The follow-up of the patients revealed surprisingly long survival spans for several patients despite high CA125 levels. To investigate the therapeutic effectiveness of OvaRex MAb-B43.13 (AltaRex, Edmonton, Canada) under well-controlled conditions, the antibody was tested in a human-PBL-SCID/BG mouse model with CA125 positive human ovarian cancer cells. Mice were reconstituted with human peripheral blood lymphocytes (PBL, normal donors) by intraperitoneal (IP) injection of 2 to 3 x 10(7) PBL/mouse. OvaRex MAb-B43.13 was administered at 100 microg/mouse in phosphate buffered saline (PBS), in three different experimental set-ups. An isotype-matched control antibody (MOPC21 or MAb-170) and PBS injection served as controls. The ovarian cancer cell line NIH:OVCAR-NU-3 was injected IP at 1 x 10(6) cells/mouse or subcutaneously (SC) at 4 x 10(6) cells/mouse. Human-PBL-SCID/BG mice were either immunized before injection of tumor cells, along with tumor cells or after small tumors were established (2 weeks after transplantation). Antibody injections were repeated twice in 2-week intervals. Functional and cellular characterization of serum and PBL from these mice demonstrated the successful engraftment of a human immune system in those mice. All three experiments showed that OvaRex MAb-B43.13 treatment could (a) delay or prevent development of tumors; (b) reduce the size of small established tumors (SC tumor injection) or suppress ascites formation; (c) delay tumor growth when injected prior to tumor implantation; and (d) prolong the survival of the mice (i.p. tumor injection).
Schultes
B C
BC
AltaRex Corp., Edmonton, Canada.
Zhang
C
C
Xue
L Y
LY
Noujaim
A A
AA
Madiyalakan
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D018394:CA-125 Antigen / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007150:Immunohistochemistry; D007167:Immunotherapy; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D018394:CA-125 Antigen; D007074:Immunoglobulin G; C107428:oregovomab