Synergistic effects of combined therapy using paclitaxel and [90Y-DOTA]776.1 on growth of OVCAR-3 ovarian carcinoma xenografts.
OBJECTIVE
776.1 is a monoclonal antibody prepared against the human ovarian cancer antigen CA 125 that demonstrates preferential binding to the cell-associated form of the antigen and has shown promising results as an yttrium-90-labeled antibody in pre-clinical studies examining the effects on tumor growth in a murine xenograft model of human ovarian cancer. The purpose of the present study was to examine the effects of combined therapy with [90Y-DOTA]776.1 and paclitaxel compared with monotherapy with either agent on the growth of OVCAR-3 xenografts in nude mice.


METHODS
Mice bearing OVCAR-3 xenografts were treated with paclitaxel alone, 50 microCi or 150 microCi [90Y-DOTA]776.1 alone, or a combination of both treatments. Control groups were included which consisted of a nonspecific antibody, MOPC-21, labeled to a similar degree, administered as monotherapy or in combination with paclitaxel. The effects of administration of radioimmunotherapy prior to or following chemotherapy were also examined.


RESULTS
Treatment with paclitaxel and [90Y-DOTA]776.1 had a synergistic anti-tumor effect on the growth of OVCAR-3 xenografts. Synergy was only observed when a tumor-specific antibody was used in radioimmunotherapy. While no difference in tumor growth was observed with order of dosing, reduced toxicity was seen when paclitaxel was administered prior to radioimmunotherapy.


CONCLUSIONS
The combination of radioimmunotherapy using an anti-CA 125 monoclonal antibody and chemotherapy with paclitaxel was shown to be effective in an in vivo model of ovarian cancer and may hold promise as a treatment regimen for patients with ovarian cancer.
Masters
Gregg R
GR
Purdue Pharma, L.P., Immunotherapeutics Department, 6 Cedar Brook Drive, Cranbury, NJ 08512, USA.
Berger
Marc A
MA
Albone
Earl F
EF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018394:CA-125 Antigen / Q000276:immunology*; D002277:Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D016499:Radioimmunotherapy; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
C515243:776.1 monoclonal antibody; D000911:Antibodies, Monoclonal; D018394:CA-125 Antigen; D018796:Immunoconjugates; D011838:Radiation-Sensitizing Agents; D015021:Yttrium Radioisotopes; D017239:Paclitaxel