Results of recent pre-clinical studies with AMF-1c-120 (Amorfix Life Sciences, Ltd) shows that this proprietary anti-ovarian cancer antibody, when administered to live animals, targets and binds to tumors in a very localized and concentrated manner. This is a significant finding because it shows that the antibody retains its tumor-specific binding in vivo.
As part of the pre-clinical study, cancer cells were examined using immunohistochemistry (IHC), combining anatomical, immunological and biochemical techniques to identify discrete tissue components by the interaction of target antigens with specific antibodies tagged with a visible label. IHC makes it possible to visualize the distribution and localization of specific cellular components within cells and in the proper tissue context.
The results showed excellent binding of the antibody specifically to its intended target, the misfolded prion proteins on the surface of the tumor.
“These remarkable results show that our technology enables one to generate antibodies that selectively bind to living tumors and not to normal cells”, noted Neil Cashman,Ph.D, CEO, Chairman and founder of Amorfix, an early-stage product development company developing therapeutic antibodies and diagnostics targeting misfolded protein diseases. “These most recent results complement our earlier studies demonstrating a significant inhibition of ovarian tumor growth in a similar ovarian cancer animal model when AMF-1c-120 is conjugated to the toxin urease, an enzyme isolated from jack beans,” he said.
Antibody-drug conjugates
The antibody – AMF-1c-120 – delivers urease directly to the tumor, where the enzyme then metabolizes urea, a by-product of amino acid degradation that is abundant in the interstitial space that separates cells. Urea forms two metabolites which stimulate cancer cell death. These metabolites are hydroxide ions, which raise the pH around the cell, and ammonium ions, which are reputedly cytotoxic and can readily diffuse into cancer cells.
This process in which an antibody delivers a drug payload to a target may bring new hope to women with ovarian cancer,the fifth most common cancer among women, and it causes more deaths than any other type of female reproductive cancer. Most deaths from ovarian cancer occur in women age 55 and older. Ovarian cancer is often not diagnosed until late-stage disease when the cancer has spread to other organs in the body, which contributes to the short survival time after diagnosis. Ovarian cancer is typically treated with surgery and chemotherapy. Chemotherapy is not very effective as a treatment and is associated with a number of potential dose-limiting side effects due to its non-specific killing of both tumor and normal cells.
Proof of concept
“We have now firmly established the proof of concept and validated the ProMIS discovery technology as a method to generate targeted therapeutics for the treatment of cancer”, said Amorfix Chief Executive Officer, Robert Gundel, Ph.D “I believe that [our] ProMIS™ discovery technology – a platform that cancer researchers can use to develop antibodies that specifically bind and kill tumors without the adverse side effects that are observed with conventional cancer treatments – is one of the most innovative and important new breakthroughs in cancer drug development. This is an exciting time for [our] as we continue to advance our therapeutic antibody programs through preclinical development”.
Pre-clinical studies
These studies were performed using the ES-2 ovarian clear cell carcinoma (OCCC) tumor model. Clear cell carcinoma accounts for 5-13% of ovarian cancer cases in Western populations and 15-25% of cases Japan. OCCC has been shown to be associated with a poorer prognosis and is relatively resistant to conventional platinum-based chemotherapy when compared to other types of ovarian cancer. Thus, there is a great need for novel OCCC therapies.
This article was first published in Onco’Zine – The International Cancer Network [Article]
