The abstracts are the result of research conducted by collaborators at the Department of Hematology, Medical University of Lodz in Poland, Alfacell and the Brander Cancer Research Institute and Department of Pathology at New York Medical College. ONCONASE and R-Amph are amphibian endoribonucleases with unique mechanisms of inhibiting the growth and causing apoptosis (programmed cell death) of malignant cells. Previously, ONCONASE has been shown to affect multiple cellular pathways involved in these mechanisms, and has been validated in many solid tumor cell lines, as well as a T-cell leukemia cell line. These reports now broaden ONCONASE's activity into CLL and AML, and include a related endoribonuclease, R-Amph.
For the study in CLL, leukemic cells were isolated from 36 untreated patients with CLL and were cultured for 24-72 hours with either ONCONASE or R-Amph alone and in combination with the purine analogues cladribine (2-CdA) and fludarabine (FA), as well as with doxorubicin. A significant cytotoxic effect of ONCONASE and R-Amph was evident after 48 and 72 hours of treatment, respectively. Synergistic activity was seen in the combination of the endonuclease plus either purine analogue. The combination of doxorubicin with ONCONASE or R-Amph demonstrated an increase in pro-apoptotic activity when compared to single agent treatment, although the effect was not statistically significant. This is the first study showing cytotoxic, pro-apoptotic effects of ONCONASE and R-Amph in CLL, and synergism with the most widely used CLL therapies.
For the study in AML, leukemic cells isolated from 22 patients with newly diagnosed AML were cultured for 24-72 hours with either ONCONASE or R-Amph alone and in combination with doxorubicin or cytarabine arabinoside. In these experiments, both endoribonucleases showed significant activity against AML cells. The main mechanism of this action was shown to be the triggering of caspase-dependent apoptosis by activation of the mitochondrial pathway. The combination of ONCONASE or R-Amph with doxorubicin in AML exhibited significant synergistic cytotoxicity, and offers insights into the potential therapeutic enhancement for doxorubicin, from a class of drugs commonly used as first line therapy in AML.
"These ex vivo studies expand the potential of ONCONASE as a potential treatment for various leukemias," said Kuslima Shogen, Alfacell's chief executive officer. "Based on our knowledge of the impact of ONCONASE on cellular pathways involved in tumor cell growth, and also in resistance to chemotherapy, additional studies may further demonstrate ONCONASE's promising anti-leukemic activity."
About AML
AML (acute myeloblastic leukemia) is a cancer of the myeloid line of white blood cells, characterized by the rapid proliferation of abnormal cells which accumulate in the bone marrow and interfere with the production of normal blood cells. AML is a potentially curable disease; but only a minority of patients are cured with current therapy. AML is treated initially with chemotherapy aimed at inducing a remission; some patients may go on to receive a hematopoietic stem cell transplant. Although cure rates have been reported to be 20-45%, this is likely to be much lower for elderly patients and those who cannot tolerate aggressive therapy.
About CLL
CLL(chronic lymphocytic leukemia) is a cancer of the lymphocytic line of white blood cells. CLL affects a particular lymphocyte, the B cell, which originates in the bone marrow, develops in the lymph nodes, and normally fights infection. In CLL, the DNA of a B cell is damaged, so that it can't fight infection, but it grows out of control and crowds out the healthy blood cells that can fight infection. While generally considered incurable, CLL progresses slowly in most cases. Determining when to start treatment and by what means is often difficult. In addition, several drugs are used to treat CLL, however Fludarabine is the most extensively studied and is currently the most commonly used first-line therapy in this disease.
About ONCONASE(R)
ONCONASE is a first-in-class therapeutic product candidate based on Alfacell's proprietary ribonuclease (RNase) technology. A natural protein isolated from the leopard frog, ONCONASE has been shown in the laboratory and clinic to target cancer cells while sparing normal cells. ONCONASE triggers apoptosis, the natural death of cells, via multiple molecular mechanisms of action.
Alfacell has licensed the U.S. commercial rights for ONCONASE to Strativa Pharmaceuticals, a division of Par Pharmaceutical, Inc. Strategic marketing and distribution agreements for ONCONASE have been secured with Megapharm Ltd. for Israel, BL&H Co. Ltd. for Korea, Taiwan and Hong Kong, USP Pharma Spolka Z.O.O., an affiliate of US Pharmacia, for Eastern Europe, and GENESIS Pharma, S.A. for Southeastern Europe.
ONCONASE has been granted fast track status and orphan-drug designation for the treatment of malignant mesothelioma by the FDA. Additionally, ONCONASE has been granted orphan-drug designation in the European Union and Australia.
About Alfacell Corporation
Alfacell Corporation is the first company to advance a biopharmaceutical product candidate that works in a manner similar to RNA interference (RNAi) through late-stage clinical trials. The product candidate, ONCONASE, is an RNase that overcomes the challenges of targeting RNA for therapeutic purposes while enabling the development of a new class of targeted therapies for cancer and other life-threatening diseases. For more information, visit
Safe Harbor
This press release includes statements that may constitute "forward-looking" statements, usually containing the words "believe," "estimate," "project," "expect" or similar expressions. Forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from the forward-looking statements. Factors that would cause or contribute to such differences include, but are not limited to, uncertainty whether the clinical trial results will allow the company to complete submission of a New Drug Application and if a New Drug Application submission is completed, uncertainty whether FDA will file or approve such application, uncertainties involved in transitioning from concept to product, uncertainties involving the ability of the company to finance research and development activities, potential challenges to or violations of patents, uncertainties regarding the outcome of clinical trials or differences of opinion in interpreting the results of clinical trials, the company's ability to secure necessary approvals from regulatory agencies, dependence upon third-party vendors, and other risks discussed in the company's periodic filings with the Securities and Exchange Commission. By making these forward-looking statements, the company undertakes no obligation to update these statements for revisions or changes after the date of this release.
Alfacell Corporation