The Rapid Reporter: June 2007

July 14, 2010
John D. Zoidis, MD

,
Diane West

OBTN, June 2007, Volume 1, Issue 5

This issue features reports from: American Association for Cancer Research meeting April 14-18, 2007 Los Angeles, CA BIO International Convention May 6-9, 2007 Boston, MA

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â–º AMERICAN ASSOCIATION FOR CANCER RESEARCH

April 14-18, 2007 Los Angeles, CA

Reports by John D. Zoidis, MD

New Research in Malignant MesotheliomaNovel Biomarkers May Make Early Detection in High-Risk Patients Possible, and Onconase May Have Potential as a Chemopreventive Agent

Ranpirnase (Onconase®) may have potential as a chemopreventive agent, according to world-renowned malignant mesothelioma (MM) researcher Michele Carbone, MD, PhD, Professor and Director of the Thoracic Oncology Program and Clinical Professor of Pathology at the University of Hawaii’s Cancer Research Center of Hawaii and Chairman of the Alfacell Thoracic Advisory Board, who moderated a series of poster presentations at the annual meeting of the American Association for Cancer Research, Los Angeles, CA, April 14-18, 2007.

Dr. Carbone highlighted the growing worldwide problem of asbestos exposure and its link to MM. He presented data showing that early detection in patients at high risk for developing MM is becoming more prevalent as a result of recently recognized biological markers, including soluble mesothelin-related protein (SMRP) and osteopontin (OPN).

Dr. Carbone and his team of investigators evaluates whether these novel biomarkers could identify MM in its early stages in high-risk persons in Cappadocia, Turkey, where 50% of all deaths are caused by MM. Fresh sera were collected from 69 healthy persons ≥30 years of age, at 3 month intervals, and compared to sera from 11 individuals with a confirmed diagnosis of MM. A separate cohort of 12-year-old frozen sera from 72 apparently healthy villagers and 8 with known MM were also analyzed. Excellent discrimination for SMRP and OPN between healthy and MM was seen. For the 12-year-old sera, the SMRP and OPN sensitivity and specificity were preserved. The investigators concluded that SMRP and OPN are ex¬traordinarily promising markers for identifying early-stage MM in high-risk cohorts.

Dr. Carbone also discussed the favorable toxicity profile and well-documented mechanism of action of Onconase, which directly affects the ubiquitin-proteasome proteolytic (UPP) pathway—the biomolecular pathway that has been shown to cause asbestos-related carcinogenesis. The elucidation of this pathway and future clinical testing may lead to the use of Onconase as a chemopreventive agent to potentially prevent the onset of MM, or reduce the doses of cytotoxic agents needed in patients who develop the disease.

According to Dr. Carbone, “The potential of Onconase as an early, first-line preventative treatment for mesothelioma is an exciting development that we plan to investigate through clinical trials. With approximately more than 25 million asbestos exposure cases reported worldwide, we believe that Onconase might play a greater role in the treatment protocols for a much larger population than was originally envisioned for this dismal disease.”

Onconase is a therapeutic product candidate based on Alfacell’s proprietary ribonuclease (RNase) technology. Onconase is a natural protein isolated from the leopard frog, and has been shown in preclinical models to target cancer cells while sparing normal cells. Onconase triggers apoptosis, the natural death of cells, via multiple molecular mechanisms of action.

Bavituximab Equivalent Generates Curative Immune Responses as Part of a Vaccine-Like Regimen in Preclinical Models of Aggressive Glioma

The results of preclinical studies evaluating the antitumor responses to 2aG4—a mouse equivalent to the Peregrine Pharmaceuticals’ antiphosphatidylserine (anti-PS) antibody bavituximab—were presented at the annual meeting of the American Association for Cancer Research, Los Angeles, CA.

Anionic phospholipids, primarily PS, become exposed on the external surface of vascular endothelial cells in tumors, providing an excellent marker for tumor vascular targeting. Dr. Jin He and colleagues at the University of Texas Southwestern Medical Center, Dallas, TX explored the possibility of enhancing the immunogenicity of irradiated glioma cells by treating them with 2aG4 in vitro.

In previous research, Dr. He and colleagues treated rats with orthotopic glioblastoma with single-fractionated radiation combined with 2aG4. The treatment resulted in a marked prolongation of survival time and some tumor cures (15%). Surviving animals were immune to intracerebral challenge with live, untreated F98 glioma cells. These findings suggested that PS on tumor cells might be suppressing the host immune response to the tumor cells and that blocking PS with 2aG4 restored immunogenicity.

In the current study, Dr. He and his team evaluated the possibility of enhancing the immunogenicity of irradiated F98 glioma cells by treating them with 2aG4 in vitro. A 57% long-term survival rate was observed in the 2aG4 group, versus a rate of 16% for rats immunized in the control antibody group. The superior survival in the 2aG4 group was statistically significant (P < 0.01). In addition, the antibody-coated F98 glioma cells were able to elicit specific T-cell responses, based on enhanced production of tumor-reactive interferon-gamma (IFN-γ)—producing T cells and increased cytotoxicity of T cells on F98 gliomas. The investigators concluded that anti-PS antibody treatment of tumor cells may enhance cross-presentation of tumor antigens as well as the generation of glioma-specific T cells by dendritic cells. Anti-PS antibody treatment might therefore be combined with radiosurgery in clinical settings to treat brain tumor patients.

The key role of the bavituximab equivalent’s anti-PS activity in protecting these animals was illustrated by the fact that a group receiving irradiated control antibodies that did not block PS only achieved a 16% long- term survival rate. These data may have profound clinical significance because the glioma cells used in the study are a highly aggressive variety, and a 2aG4 vaccine-like regimen resulted in a strong immune response to the cancer, which was not seen in the controls.

Steven W. King, President and CEO of Peregrine, remarked, “These exciting data suggest a potential new application for bavituximab and our anti-PS antibody platform as part of a cancer vaccine regimen that aims to restore the ability of the patient’s own immune system to recognize and fight cancer. Based on these promising results, we are continuing our evaluation of these vaccine-like regimens containing bavituximab for potential application to a variety of cancers.”

Bavituximab is a targeted monoclonal antibody that binds to a PS, which is normally located on the inside of cells, but which becomes exposed on the outside of the cells that line the blood vessels of tumors. Once bound to tumor blood vessels, bavituximab alerts the body’s immune system to attack the blood supply of the tumor, thereby resulting in tumor-cell death. PS blockers may have the potential to help reverse this suppression and enable the immune system to attack the cancer more effectively. As an anticancer immunotherapeutic agent, bavituximab may have broad potential in a wide variety of solid cancers. It is currently in Phase Ia cancer safety trials as monotherapy and in a Phase Ib trial in combination with docetaxel and other chemotherapy agents in patients with advanced solid cancers, including carcinoma of the prostate, breast, and lung.

â–º BIO International Convention

May 6-9, 2007 Boston, MA

Reports by Diane West

Survey: Biotech-Based Disease Cures “A Top National Issue”General Public and Biotech Leaders View Curing Disease More Urgent than Terrorism, Immigration Issues

National security concerns, including terrorism and illegal immigration, take a back seat when it comes to finding cures for cancer and other serious diseases, according to a recent nationwide survey of public citizens and leaders in the biotech industry.

The findings were announced at the May 2007 BIO International Convention held in Boston this year.

According to the survey, conducted by the Public Opinion Strategies and Peter D. Hart Research Associates groups, 78% of 800 registered U.S. voters who participated in a telephone poll this spring considered finding cures for serious diseases such as cancer, Parkinson’s, Alzheimer’s, HIV/AIDS and MS a “top national issue.” Concern over this issue was tied with improving public education, followed closely by improving the economy and job creation (77%). Defending the country against terrorism and stemming illegal immigration came in fourth at 71%. The survey had a margin of error of 3.5%.

“The results of this poll show strong public support for our industry,” according to Biotechnology Industry Organization president Jim Greenwood. The survey results, he added, were consistent with the 2007 meeting’s theme: “New Ideas. Bold Ventures. Global Benefits.”

Oncology-related patient and health advocacy groups represented at the Convention included the American Association for Cancer Research, The Leukemia & Lymphoma Society, the National Breast Cancer Coalition Fund and the Prostate Health Education Network.

Understanding of Biotech, Cost of Access Impacts Public Opinion

Only 45% of public survey participants initially said they viewed the field of biotechnology “favorably”, but this figure shot up to 86% when participants were told biotechnology had the potential to extend the quality of life for patients with serious disease like cancer. Additionally, 80% of the public survey respondents said full access to biologically—engineered medicines should be extended to Medicare and Medicaid patients. Fourteen percent viewed the increased cost to the government of providing this kind of universal access to advanced treatments as “troubling.” (Notably, 54% of the public respondents were male and earning more than $100K per year).

Biotech Leaders Interested in Curing Disease, Keeping Government Regs Out

Much like the public survey participants, some 2,000 biotech professionals surveyed indicated a strong interest in finding cures for serious diseases, with 94% saying they were optimistic about finding cures for many within the next two decades. However, a majority of biotech leaders think “regulatory burdens” (i.e., government oversight) would impede their progress, with 71% indicating they want government to stay out of innovation whenever possible, including such controversial topics as stem cell research. Still, 59% of industry leaders said they want increased federal funding for biomedical research.

The four-day 2007 BIO International Convention drew over 22,000 attendees from almost all states in the U.S. and 64 countries worldwide; one-third conference attendees hailed from outside of the U.S. Attendance was up almost 15% from the previous year and included keynote speakers such as actor Michael J. Fox, who founded the Michael J. Fox Foundation for Parkinson’s Research several years after being diagnosed with the condition himself, and Queen Noor of Jordan, whose husband, King Al-Hussein of Jordan, died in 1998 after a battle with non-Hodgkin’s lymphoma.

Biotech Leader Calls Patient, Industry Support The “Only Way” To Combat Cancer

President of BIO says government must support research without overly zealous regulation of the industry if cancer cures are to be discovered

The head of an industry organization representing over 1,000 biotechnology companies, academic institutions, and other affiliates worldwide says patients, scientists, and industry must support a political environment conducive to drug discovery if diseases like cancer are to be beaten.

Oncology & Biotech News

“Continued innovation is the only way to make progress against cancer,” James C. Greenwood, president and CEO of the Biotechnology Industry Association told . “Physicians, biomedical innovators and patients need to advocate for a regulatory environment that supports innovation through strong intellectual property protection, access to investment capital and fair pricing to enable innovators to recover development costs and invest in new research.”

Mr. Greenwood’s comments come as the fight for the presidency of the United States in 2008 is well underway, with topics such as stem-cell research and vaccines against sexually transmitted cancers often making their way into debates among candidates.

A regulatory environment which both invests in discovery while not imposing heavy regulation of the industry will, Mr. Greenwood says, lead to ground-breaking cancer cures. “Emerging advances will soon enable us to place nanoparticles inside tumors to image and attack tumors,” he says. Additionally, he says “advances in gene therapy will enable scientists to ‘switch off’ cancer cells, and “nanosensors will enable us to simultaneously test for hundreds or even thousands of different biomolecules in a drop of blood.”

The record-breaking turnout and panel discussions at May’s BIO 2007 meeting, Mr. Greenwood says, “demonstrated that biotechnology innovation continues to completely reinvent cancer prevention, detection and treatment, moving us ever closer to our vision of making cancer obsolete.”