Preliminary results of nanopharmaceuticals used in the radioimmunotherapy of ovarian cancer.
OBJECTIVE
The treatment of late stage ovarian cancer presents an unmet clinical need for women around the world. A multistep radioimmunotherapeutic (RIT) approach, exploiting the combination of a bispecific monoclonal antibody (BsMAb) with 90Y labelled biotinylated long-circulating liposomes was tested as a potential adjuvant treatment for epithelial ovarian carcinomatosis in an attempt to meet this need. This approach was used to overcome some of the major obstacles associated with conventional strategies, in particular, to increase the amount of radioactivity delivered to the tumor site compared with conventional monoclonal antibody (MAb) radionuclide delivery. We hypothesize that sequential intraperitoneal administration of the targeting and therapeutic moieties provides the basis for an enhanced therapeutic ratio.


METHODS
A BsMAb, with anti-CA 125 and anti-biotin epitopes was engineered for use with PEGylated liposomes coated with biotin to deliver the cytotoxic radionuclide 90Y to tumor sites. An in vivo therapy trial was used to test this RIT protocol with Balb/c nude mice (n=29) xenografted with the NIH:OVCAR-3 (CA 125+) human ovarian cancer cell line.


RESULTS
A median tumor growth delay of 91 days for the combined treatment group versus 77.7 days for the control group was observed.


CONCLUSIONS
An ongoing tumor growth delay/control study using this model has indicated an appreciable delay in progress of tumor and ascites development in treated vs. control populations.
McQuarrie
Steve
S
Faculty of Pharmacy and Pharmaceutical Sciences, Noujaim Institute for Pharmaceutical Oncology Research, University of Alberta, Edmonton, Alberta, Canada. steve.mcquarrie@ualberta.ca
Mercer
John
J
Syme
Alasdair
A
Suresh
Mavanur
M
Miller
Gerald
G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000970:Antineoplastic Agents; D008081:Liposomes