Ludwig Institute for Cancer Research

(New York, January 1, 2009) – Investigators from the Ludwig Institute for Cancer Research (LICR) Melbourne Center reported today in the journal The Prostate that a potential new reagent could treat prostate tumors with greater specificity and reduced toxicity than many currently used therapies. The reagent, 177Lu-hu3S193, is based on a modality known as radioimmunotherapy (RIT), which uses antibodies to deliver lethal doses of radiation specifically to tumor cells.

The study demonstrated that the 177Lu-hu3S193 RIT specifically targeted androgen-independent human prostate tumors that had been generated in mice, and stunted the growth of the tumors. The anti-tumor activity of the RIT was further enhanced when combined with a chemotherapy or an inhibitor of a cell-surface receptor, EGFR, that transmits growth-promoting signals to the cell.

The American Cancer Society estimates that more than 186,300 cases of prostate cancer will be diagnosed in 2008. While early-stage prostate cancer can be treated with great success, patients with advanced disease that has metastasized are in need of new, targeted therapies. According to the study’s senior author, Andrew Scott, MD, Director of the LICR Melbourne Center, the 177Lu-hu3S193 RIT tested in this study has potential to selectively target both primary tumors and metastases to effectively kill the cancer cells. “The specific targeting of the hu3S193 antibody to cancer cells, no matter where they are found in the body, makes this a particularly promising approach for metastatic cancer that will have less toxic side-effects.”

The hu3S193 antibody, developed by LICR scientists at the New York Branch and Melbourne Center, binds with great specificity to a protein, called the Ley antigen, located on the cell surface of the majority of prostate and many other cancers. Previous clinical studies conducted by Dr. Scott and his colleagues in patients with breast, colorectal, and small cell lung cancers demonstrated that the hu3S193 antibody selectively targeted the tumor cells and was well-tolerated by the patients. Lutetium-177 (177Lu) was chosen as the radioactive payload because its physical properties correlate well to small tumors and metastases, allowing maximal killing of cancer cells while sparing healthy neighboring cells. An unconjugated version of the hu3S193 antibody is now in clinical development with an LICR spin-off company, the Brazilian biotechnology company, Recepta Bipharma.

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This study was authored by MP Kelly (LICR), ST Lee (LICR), F-T Lee (LICR), FE Smyth (LICR), ID Davis (LICR), MW Brechbiel (National Cancer Institute), and AM Scott (LICR).