Jim Black is fighting the meanest, most aggressive, most common kind of brain Tumor in the United States: recurrent Glioblastoma Multiforme (GBM). In the United States, each year, approximately 10,000 patients are affected by GBM. Now, a novel investigational device – available only at clinical trial sites – is offering new hope to these patients.
The non-invasive procedure – called Tumor Treating Fields (TTF) – is delivered using a portable device – called the NovoTTF-100A System made by Novocure. The TTF procedure uses alternating electrical fields to disrupt the rapid cell division exhibited by cancer cells.
"Patients with recurrent GBM present a significant treatment challenge," said Santosh Kesari, MD, PhD, director of Neuro-Oncology at UC San Diego Moores Cancer Center. "The initial clinical research for the approval trial demonstrated that, compared to patients who were treated with Chemotherapy, patients treated with NovoTTF achieved comparable survival times, had fewer side effects, and reported improved Quality of life."
On average, a patient with GBM survives less than 15 months with optimal treatment and only three to five months without additional effective treatment. The TTF procedure may provide physicians with a fourth treatment option in addition to surgery, radiation therapy and chemotherapy.
TTFs inhibit tumor growth by causing cancerous cells to die. The TTF procedure is delivered using non-invasive, insulated transducer arrays (electrodes) that are placed directly on the skin in the region of the tumor. The hat-like collection of electrodes connects to a portable device which is slightly thicker than a laptop and weighs about six pounds. The device sends a low intensity, alternating electric field into the tumor which prevents the cells from dividing and spreading and causes cancer cells to die.
The most commonly reported side effect from NovoTTF is a mild-to-moderate scalp rash, beneath the electrodes. The FDA-approved device is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted.
"When all other options have been exhausted, patients are willing to do just about anything to keep the tumor at bay," said Kesari. "This device gives them an opportunity to fight back, to feel like they are taking an active, hands-on role in their own treatment, and provides tremendous hope."
Study Published in Neuro-Oncology Journal Shows Brain Tumor Eradication and Prolonged Survival in Mice Treated With Toca 511 and 5-FC
Friday, 03 February 2012 15:32
SAN DIEGO, Feb. 3, 2012 /PRNewswire/ -- Tocagen Inc. today announced the publication of data showing the company's investigational treatment for high grade Glioma eradicates brain tumors and provides a dramatic survival benefit in mouse models of glioblastoma. Almost all mice receiving the top dose of Toca 511 followed by 5-FC were still alive at 180 days, which was the termination date for the experiment, whereas all control mice died by day 43. The article was published today in the February issue of the Neuro-Oncology journal.
"After administration of Toca 511, the efficiency and specificity of viral spread through the Tumor in an immune-competent animal model was impressive," said John Coffin, Ph.D., American Cancer Society Professor at the Sackler School of Biomedical Sciences at Tufts University and Special Advisor to the Director, HIV Drug Resistance Program, Center for Cancer Research, National Cancer Institute. "As a career retrovirologist and advisor to the scientists at Tocagen, I am pleased to see the progress they have achieved with their retroviral replicating vector technology, and I look forward to seeing how this approach translates in humans with advanced cancer."
The results published in Neuro-Oncology showed that Toca 511 delivers a pro-drug activating gene to tumor cells where it converts the pro-drug 5-FC (flucytosine) into the anti-cancer drug 5-fluorouracil. Treatment with the high doses of Toca 511 resulted in elimination of tumors in most animals after dosing with 5-FC. The combination treatment of Toca 511 and 5-FC was well tolerated and did not cause toxicity over the course of the six month treatment protocol.
"Because of the invasive nature of glioblastoma, cancer cells are typically left behind after surgery, even with a 'complete' resection, making tumor re-growth almost inevitable," said Santosh Kesari, M.D., Ph.D., director of Neuro-Oncology in the Moores Cancer Center and in the Department of Neurosciences at the University of California, San Diego, one of the investigators in the Toca 511 clinical study. "There is an urgent need for new treatments that can eliminate residual cancer cells in patients with glioblastoma and other invasive gliomas. These preclinical results are very promising and provided the support for initiating human clinical trials of Toca 511."
About Toca 511 & Toca FC
The combination of Toca 511 (vocimagene amiretrorepvec), for injection & Toca FC (flucytosine), extended-release tablets is being investigated at leading centers across the US in clinical studies in patients with recurrent high grade glioma, including Glioblastoma Multiforme (GBM). Toca 511 is a retroviral replicating vector (RRV) that is designed to deliver a prodrug activator gene called cytosine deaminase (CD) selectively to cancer cells. After allowing time for Toca 511 to spread through the tumor, those cancer cells expressing the CD gene can convert the anti-biotic drug flucytosine into the anti-cancer drug 5-fluorouracil (5-FU). In these studies, patients receive a single administration of Toca 511 at the time of surgery ( Craniotomy or biopsy) followed by multiple cycles of oral Toca FC.
About Tocagen
Tocagen Inc. is a privately funded, clinical stage biopharmaceutical company pursuing the discovery, development and commercialization of gene transfer products for the treatment of cancer. Tocagen is initially focusing on treatments for patients with advanced cancer for whom no adequate treatments currently exist. Toca 511, the company's lead investigational product candidate, is being evaluated in clinical trials in patients with recurrent high grade glioma (such as glioblastoma multiforme). Tocagen has received grant support from leading brain cancer foundations including, Accelerate Brain Cancer Cure (ABC2), the American Brain Tumor Association (ABTA), and the National Brain Tumor Society (NBTS). For more information about Tocagen or Toca 511 please visit www.tocagen.com or www.clinicaltrials.gov.
Dendritic cell vaccine, manufactured in unique RPCI facility, trains body’s defenses to remember, destroy cancer cells
Wednesday, 01 February 2012 21:28
Last Updated ( Wednesday, 01 February 2012 21:31 )
The Center for Immunotherapy at Roswell Park Cancer Institute (RPCI) has launched a phase I clinical research study of a dendritic cell vaccine designed to both eradicate Cancer cells and prevent disease relapse. Developed at RPCI, the NY-ESO-1 dendritic cell vaccine will be manufactured in the Institute’s new Therapeutic Cell Production Facility using a unique FDA-approved process — making RPCI the first research facility in the U.S. to use a custom-made barrier isolator for vaccine cell production, and the first in the world to use this system in an approved, government-regulated study.
Dendritic cells are the gatekeepers of the human Immune System, defending against invaders like bacteria, viruses and cancer. The vaccine to be produced at RPCI will be the first to incorporate a particular form of NY-ESO-1, antiDEC205-NY-ESO-1. “Armed with this specialized protein, the treated cells are then given back to the patient as a vaccine designed to recruit an army of killer immune cells that seek out and destroy cancer,” explains Kunle Odunsi, MD, PhD, Director of RPCI’s Center for Immunotherapy (CFI) and the study’s Principal Investigator.
The new study is also unique in that it’s the first to test a dendritic vaccine given in combination with rapamycin, a compound used to prevent rejection of solid-organ transplant. The study just launched will capitalize on a striking recent scientific discovery by Protul Shrikant, PhD, of the Department of Immunology at RPCI, who found that in low doses, rapamycin confers a previously unknown benefit — it prevents the immune system from using up its cancer-killing T-cells in one quick burst. “We have shown for the first time that rapamycin has the capacity to produce immune cells that have memory attributes,” explains Dr. Odunsi, who is also Chair of RPCI’s Department of Gynecologic Oncology. “The immune cells are trained to live longer and to always remember that cancer cells are bad and should be attacked and killed.”
The ability to stretch out the attack for a long-term, durable response suggests that the vaccine may be effective in preventing disease recurrence. The new NY-ESO-1 dendritic cell vaccine is expected to show great promise in patients with bladder, brain, breast, esophageal, gastrointestinal, hepatocellular, kidney, lung, melanoma, ovarian, prostate, sarcoma and uterine tumors.
The NY-ESO-1 vaccine, tailor-made for each patient, will be produced in RPCI’s Therapeutic Cell Production Facility (TCPF) under the direction of Yeong “Christopher” Choi, PhD, who notes: “We believe that our facility’s custom-made barrier isolator, the unit in which the vaccines are manufactured, is the first of its kind.” The barrier isolator — an Xvivo System processing chamber designed to RPCI’s specifications by BioSpherix, Ltd., Lacona, NY — maintains strict control of the unit’s temperature and atmospheric gases, critical for optimal production of dendritic cell vaccines.
“Those conditions, and the sterile vaccine-manufacturing environment, are rigidly maintained throughout the entire process,” says Dr. Choi. “The Xvivo — which at about 70 square feet is basically a clean room in a box — acts as a physical barrier that protects the cell-therapy product from outside contaminants, resulting in a safer, more predictable manufacturing process.”
The potential of therapeutic vaccines is attracting increasing interest in the field of oncology. Last year, the FDA approved the first therapeutic cancer vaccine, Provenge® (sipuleucel-T), for men with advanced prostate cancer. RPCI’s Center for Immunotherapy is awaiting FDA approval to launch additional cancer vaccine trials, including a vaccine for Malignant Glioma (a type of brain Tumor) and another vaccine for patients with ovarian, fallopian tube, and primary peritoneal cancer.
“This trial will be only the beginning of a very robust program of activity in the area of using the human immune system to fight cancer,” adds Dr. Odunsi. “Our production process holds tremendous potential for applications related to stem-cell therapy and regenerative medicine, and I believe we’re uniquely positioned at RPCI to have the tools, infrastructure and multidisciplinary collaboration to capitalize on these ideas and opportunities both effectively and efficiently.”
The clinical research study will enroll 18-20 eligible patients whose tumors express a specific antigen, known as NY-ESO-1. Apart from the adult male testis, NY-ESO-1 is not expressed in normal tissues of the body, but is expressed in cancers. This may help decrease the risk of side effects from the vaccine, because it should target only the tissues that express NY-ESO-1.
Dr. Odunsi, who developed the NY-ESO-1 vaccine, led previous trials evaluating its effectiveness in treating ovarian cancer. Christine Sable of Lancaster, Pennsylvania, enrolled on one of those studies in February of 2004, after undergoing surgery and Chemotherapy for advanced-stage ovarian cancer. Although she faced a 75-80% chance that the cancer would return, her immune system responded strongly to the vaccine, and she has remained cancer-free in the seven years since then, with no side effects.
To learn more about the clinical research studies of the NY-ESO-1 dendritic cell vaccine, call 1-877-ASK-RPCI (1-877-275-7724).
The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. RPCI, founded in 1898, was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit RPCI’s website at http://www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
.
A thought-provoking new therapeutic target for brain cancer?
Wednesday, 01 February 2012 21:21
Glioblastoma Multiforme (GBM) is the most common of all Malignant brain tumors that originate in the brain. Patients with GBM have a poor Prognosis because it is a highly aggressive form of Cancer that is commonly resistant to current therapies. New therapeutic approaches are therefore much needed. Joanna Phillips, Zena Werb, and colleagues, at the University of California, San Francisco, have now identified a potential new therapeutic target for the treatment of GBM.
A substantial proportion of GBMs show evidence of abnormal activation of signaling pathways triggered by a cell surface protein known as PDGFR-alpha, and this is thought to drive the Tumor. PDGFR-alpha triggers activation of signaling pathways when it binds the growth factor PDGF. Phillips, Werb, and colleagues found that the protein SULF2, which is known to regulate the availability of growth factors such as PDGF, was expressed in primary human GBM tumors and cell lines. Moreover, GBMs characterized by abnormal activation of signaling pathways downstream of PDGFR-alpha showed the strongest SULF2 expression. Importantly, knocking down expression of SULF2 in human GBM cell lines decreased the growth of these cells upon transplantation into mice. Phillips, Werb, and colleagues therefore suggest that SULF2 is a candidate therapeutic target for the treatment of GBM and that assessing its levels could identify tumors dependent on growth factors such as PDGF. The latter is important as PDGFR-alpha and other molecules to which growth factors bind are themselves good therapeutic targets.
###
TITLE: Heparan sulfate sulfatase SULF2 regulates PDGFR-alpha signaling and growth in human and mouse malignant Glioma
AUTHOR CONTACT: Joanna J. Phillips University of California, San Francisco, San Francisco, California, USA. Phone: 415.514.4929; Fax: 415.514.9792; E-mail:
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
.
Zena Werb, University of California, San Francisco, San Francisco, California, USA. Phone: 415.476.4622; Fax: 415.476.4565; E-mail:
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
.
DALLAS – Jan. 26, 2012 – Researchers at UT Southwestern Medical Center have developed what they believe to be the first clinical application of a new imaging technique to diagnose brain tumors. The unique test could preclude the need for surgery in patients whose tumors are located in areas of the brain too dangerous to biopsy.
This new magnetic resonance spectroscopy (MRS) technique provides a definitive diagnosis of Cancer based on imaging of a protein associated with a mutated gene found in 80 percent of low- and intermediate-grade gliomas. Presence of the mutation also means a better Prognosis.
"To our knowledge, this is the only direct metabolic consequence of a genetic mutation in a cancer cell that can be identified through noninvasive imaging," said Dr. Elizabeth Maher, associate professor of internal medicine and neurology at UT Southwestern and senior author of the study, available online in Nature Medicine. "This is a major breakthrough for brain Tumor patients."
UT Southwestern researchers developed the test by modifying the settings of a magnetic resonance imaging ( MRI) scanner to track the protein's levels. The data acquisition and analysis procedure was developed by study lead author Dr. Changho Choi, associate professor of the Advanced Imaging Research Center (AIRC) and radiology. Previous research linked high levels of this protein to the mutation, and UT Southwestern researchers already had been working on MRS of gliomas to find tumor biomarkers.
"Our next step is to make this testing procedure widely available as part of routine MRIs for brain tumors. It doesn't require any injections or special equipment," said Dr. Maher, medical director of UT Southwestern's neuro-oncology program.
To substantiate the test as a diagnostic tool, biopsy samples from 30 Glioma patients enrolled in the UT Southwestern clinical trial were analyzed; half had the mutation and expected high levels of the protein. MRS imaging of these patients had been done before surgery and predicted, with 100 percent accuracy, which patients had the mutation.
For Thomas Smith of Grand Prairie, the test helped determine the best time to begin Chemotherapy. When an MRS scan showed a sharp rise in the 25-year-old's protein levels, this indicated to his health care team that his tumor was moving from dormancy to rapid growth.
"We treated him with chemotherapy and his protein levels came down," Dr. Maher said.
Before participating in the study, Mr. Smith had tumor removal surgery in 2007. Because part of the tumor could not be safely removed, however, he continued to suffer seizures and had other neurological problems. Since chemotherapy, his symptoms have diminished.
"I did six rounds of chemo, every six weeks," Mr. Smith said. "My seizures stopped and all my symptoms improved. I am only on anti- Seizure medication now."
###
Other UT Southwestern researchers involved in the study included Sandeep Ganji, a doctorate student in radiological sciences; Dr. Ralph DeBerardinis, assistant professor of pediatrics and with the Eugene McDermott Center for Human Growth and Development; Dr. Kimmo Hatanpaa, associate professor of pathology; Dr. Dinesh Rakheja, assistant professor of pathology; Dr. Zoltan Kovacs, assistant professor in the AIRC; Drs. Xiao-Li Yang and Tomoyuki Mashimo, both senior research scientists in internal medicine; Dr. Jack Raisanen, professor of pathology; Dr. Isaac Marin-Valencia, resident in pediatrics; Dr. Juan Pascual, assistant professor of neurology and neurotherapeutics, pediatrics, and physiology; Dr. Christopher Madden, associate professor of neurological surgery; Dr. Bruce Mickey, professor of neurological surgery and otolaryngology-head and neck surgery, and radiation oncology; Dr. Craig Malloy, professor in the AIRC and of internal medicine and radiology; and Dr. Robert Bachoo, assistant professor in neurology and neurotherapeutics, and internal medicine.
The research was supported by grants from the National Institutes of Health, the Cancer Prevention and Research Institute of Texas and financial support from the Annette G. Strauss Center for Neuro-oncology at UT Southwestern.
Tumor in the United States: recurrent 