The National Research Council Biotechnology Research Institute (NRC-BRI) granted Alethia Biotherapeutics exclusive, worldwide diagnostic rights to a peptide that specifically binds to tumor-associated clusterin. The peptide will be the basis for development of a new molecular imaging tool that may be able to accurately detect tumor-associated clusterin in cancer patients.
This transaction with the NRC-BRI follows a previous license agreement concluded in October 2007 concerning a family of mAbs that bind specifically to tumor-associated clusterin. Clusterin secreted from cancer cells has recently been identified as a potent inducer of the epithelial-to-mesenchymal transition (EMT), a process that contributes to metastatic invasion of tumors. The lead mAb product, AB-16B5, is currently in preclinical development in several animal models of metastatic cancer including invasive breast cancer and hormone-resistant prostate cancer.
"With the perspective of initiating clinical studies in the near future, we felt it was important to undertake the development of a companion diagnostic test with the goals of accurately identifying the cancer patients who would benefit the most from an anticlusterin-based therapy and monitoring of response to treatment,” says Mario Filion, Ph.D., executive vp and CSO of Alethia.
The ability of the peptide, designated P3378, to specifically home to and image tumors in vivo when fluorescently labeled with a near-infrared probe was demonstrated by real-time imaging on live tumor-bearing mice.
To date studies revealed that treatment of tumor-harboring mice with AB-16B5 reduced the growth of tumors in combination with chemotherapy. These findings support the predicted role of tumor-associated clusterin as a potent inducer of chemo-resistance in tumor cells.
Additionally, AB-16B5 effectively reduced the spread of tumor cells to secondary organs such as the lungs and the bones, confirming the ability of this anti-clusterin mAb to inhibit EMT in vivo.
“The concept that EMT is an important cellular mechanism leading to tumor progression is now widely accepted,” says Dr. Filion. “Tumor-associated clusterin is emerging as one the most specific regulators of EMT, and AB-16B5 is one of the rare therapeutic mAbs that directly targets this important biological process.
“Its therapeutic effects hold much promise to control metastasis from breast and prostate tumors in addition to enhancing the response to chemotherapeutic drugs. With the recent progress accomplished in this therapeutic program, Alethia is now at the doorstep of IND filing.”