Immunomedics has presented at the 2007 Annual Meeting of the American Association for Cancer Research results on the in vitro and in vivo evaluation of a novel immunotoxin, Rap-hRS7, for the potential treatment of prostate and lung cancers.
The in vitro cytotoxicity of Rap-hRS7 on Calu-3 human lung and PC-3 human prostate cancers was 50- and 30-fold higher than free RNase, and 10- to 20- fold more potent than an irrelevant immunotoxin. When given as a single dose of 50-micrograms to mice bearing the Calu-3 human lung cancer cell line, Rap-hRS7 was able to almost double the median survival time (96 vs. 55 days) compared to the untreated group. Similar therapeutic efficacy was observed in animals given two 25-microgram doses one week apart.
Rap-hRS7 was constructed by fusing an amphibian RNase to hRS7, an internalizing humanized antibody targeting epithelial glycoprotein-1 (EGP-1), which is expressed in high amounts in certain human cancer cell lines such as PC-3 of prostate cancer, Calu-3 of non-small-cell lung cancer, and ME180 of cervical cancer, as well as similar patient tumor specimens.
"These encouraging results provide a rationale for the further development of Rap-hRS7 as a therapy for prostate, lung and other EGP-1 expressing cancers," commented Cynthia L. Sullivan, President and Chief Executive Officer. "We plan to introduce this recombinant immunotoxin into the clinic for the therapy of prostate and lung cancers. In addition to Rap-hRS7, the hRS7 antibody provides us the opportunity to study the impact on prostate and lung cancers of a number of conjugated compounds," Ms. Sullivan remarked.
hRS7 is a humanized monoclonal antibody proprietary to Immunomedics that targets epithelial glycoprotein-1 (EGP-1), which has higher expression in prostate, lung, breast, ovarian, and cervical cancers as compared to normal tissues. The antibody has also been shown to internalize into cancer cells, making it a suitable candidate for delivery of cytotoxic drugs. By conjugating the RNA-degrading enzyme, RNase, to the humanized antibody targeting EGP-1, scientists at Immunomedics have demonstrated selective killing of cancers expressing the EGP-1 biomarker, including prostate and lung cancers. Immunomedics has been granted patents and has many pending patents covering the construction and use of RNase-bearing antibodies for the therapy of cancer and other diseases.