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News Article | November 17, 2016
Site: www.eurekalert.org

CINCINNATI--Researchers at the University of Cincinnati (UC) have discovered that an ion channel, active within T cells (white blood cells), could be targeted to reduce the growth of head and neck cancers. This research, which was reported this month in Cancer Research, shows that defective Kv1.3 channels, which regulate calcium ions (Ca2+) presence in T cells, and Ca2+ abnormalities in tumor infiltrating lymphocytes--cells that attack and kill cancer cells--may contribute to the inability of the immune system to fight off head and neck cancers. By regulating their expression at the cellular level and using the body's own immune response to fight the tumor cells, patients with these cancers could have better, more effective outcomes. "Head and neck squamous cell carcinoma is the sixth most common type of cancer, with a 5-year survival of 50 percent," says Laura Conforti, PhD, professor in the Department of Internal Medicine at the UC College of Medicine, a researcher within the UC Cancer Institute and corresponding author on the study. "The heterogeneity of these tumors, the complex anatomy of the head and neck region and the proximity of these tumors to several vital organs and structures present a challenge in conventional treatment options of these cancers. "Immunotherapies aimed to boost the immune system to fight cancer cells are showing promising results in this group of patients." Conforti says that to survive and spread, tumors create a cozy microenvironment where they often go unrecognized by the immune system. "The extent to which CD8+ cells, a type of T cell capable of killing cancer cells, infiltrate the head and neck tumor affects disease progression and responsiveness to therapy," she says. "Also, how well CD8+ lymphocytes function within the confines of the tumor microenvironment determines their ability to eradicate cancer cells, and in the case of head and neck solid tumors, tumor infiltrating lymphocytes have multiple functional defects, decreasing their ability to work correctly." "The function of CD8+ lymphocytes depends on Ca2+, which is controlled by ion channels. In particular, Kv1.3 ion channels regulate Ca2+ influx into T cells. In this study, we assessed the role of Kv1.3 channel and Ca2+ fluxes on these lymphocytes' function in head and neck cancer," she adds. Conforti says that her team, led by Ameet Chimote, PhD, research associate in the Division of Nephrology and Hypertension, used tumor samples and blood from 14 patients with head and neck cancers to analyze how Kv1.3 effected the function of tumor infiltrating T lymphocytes. They found a 70 percent reduction in functional Kv1.3 channels in tumor infiltrating lymphocytes as compared to the blood T cells, which was accompanied by a decrease in Ca2+ levels and reduced ability to attack and kill cancer cells. "Overall our data showed that suppression of Kv1.3 channels in these lymphocytes, the cells that fight off cancer, contribute to their decreased function, raising the possibility that this channel may be used as a potential marker of functionally competent T cells that have infiltrated the tumor mass," Conforti says. "These findings are particularly timely as a recently published study in Nature proposes these channels as potential new target for immunotherapy in cancer. The authors in this study reported that overexpressing these channels in an animal model with cancer lead to increased survival. "Further studies are needed on this T cell channel to find out more about its effects on head and neck cancer and ways we can target it to improve outcomes." This work was funded by grant support from the National Institutes of Health (Grant R01CA95286) and a pilot grant from the University of Cincinnati Cancer Institute and was done in collaboration with Trisha Wise-Draper, MD, PhD, assistant professor in the Division of Hematology Oncology at the UC College of Medicine, a member of both the Cincinnati Cancer Center and UC Cancer Institute, and Keith Casper, MD, a former UC faculty member who is now at the University of Michigan.


News Article | January 8, 2016
Site: www.biosciencetechnology.com

An international research team formed by a University of Cincinnati (UC) cancer researcher has shown for the first time that a specific enzyme is responsible for sensing the available supply of GTP, an energy source that fuels the uncontrolled growth of cancer cells. The research underscores the enzyme's potential to become a therapeutic target for future cancer drugs. The findings of Atsuo Sasaki, Ph.D., assistant professor in the Division of Hematology Oncology at the UC College of Medicine and a researcher at the Brain Tumor Center at the UC Neuroscience Institute and UC Cancer Institute, together with Toshiya Senda, PhD, professor at the High Energy Accelerator Research Organization in Tsukuba, Japan, were published online Jan. 7 in the journal Molecular Cell. Sasaki and fellow researchers showed that the enzyme PI5P4Kβ (phosphatidylinositol-5-phosphate 4-kinase-β) acts like the arrow on a fuel gauge. The enzyme senses and communicates (signals), via a second messenger, the amount of GTP fuel that is available to a cell at any given time. Until now, the molecular identity of a GTP sensor has remained unknown. "Energy sensing is vital to the successful proliferation of cancer cells," he says. "A large amount of GTP is required in rapidly dividing cells, and cells need to know that the fuel is available to them. If we can interfere with the ability of PI5P4Kβ to sense fuel availability and communicate that information, we may be able to slow or halt the growth of cancers, including the aggressive brain cancer glioblastoma multiforme and cancers that have metastasized to the brain." The publication in Molecular Cell is Sasaki's first to address PI5P4Kβ as a molecular sensor of GTP concentration. Initially, he and his team faced skepticism regarding the existence of GTP energy-sensing; however, with a pilot grant funded by Cincinnati's Walk Ahead for a Brain Tumor Cure and other local sources, the researchers were able to pursue their high-risk research and acquire enough promising data to earn a five-year, $1.67 million grant from the National Institutes of Health in 2014. "The publication in Molecular Cell is another milestone for Atsuo Sasaki and the UC Brain Tumor Center," says Ronald Warnick, MD, medical director of the Brain Tumor Center and the John M. Tew, Jr., Chair in Neurosurgical Oncology. "The seeds of this discovery, which were planted locally by friends of the UC Brain Tumor Center and nourished by federal tax dollars, are now bearing their first fruit as we gain a better understanding of cancer's energy mechanisms." GTP--guanosine triphosphate--is one of two energy molecules used by cells. The other is ATP (adenosine triphosphate). ATP handles the bulk of a cell's energy requirements, while GTP is required for protein synthesis and is a signaling molecule that helps direct processes within the cell. When GTP levels are increased and utilized as fuel by rampaging cancer cells, its ability to perform its primary goals is compromised. Sasaki and his team identified PI5P4Kβ as a GTP sensor by demonstrating, in a laboratory setting, its ability to bind to GTP and by demonstrating, at the atomic level by X-ray structural analysis, the molecular mechanism by which it recognizes GTP. They then designed PI5P4Kβ mutant cells that were unable to sense GTP concentration and, as a result, impaired the ability of PI5P4Kβ to promote tumor growth. His next step is to use both pharmacological and molecular approaches that target PI5P4Kβ in a cell culture and in animal tumor models. "By unveiling PI5P4Kβ's role as a GTP sensor, we now have a potential new therapeutic target for patients," Sasaki says. "If we can find drugs that stop PI5P4Kβ from acting as the fuel indicator, we could get these aggressive and tragic cancers into energy-depleted status."


Home > Press > Cedars-Sinai, UCLA Scientists Use New ‘Blood Biopsies’ With Experimental Device to Speed Cancer Diagnosis and Predict Disease Spread: Leading-Edge Research Is Part of National Cancer Moonshot Initiative Abstract: A team of investigators from Cedars-Sinai and UCLA is using a new blood-analysis technique and tiny experimental device to help physicians predict which cancers are likely to spread by identifying and characterizing tumor cells circulating through the blood. The investigators are conducting “liquid biopsies” by running blood through a postage-stamp-sized chip with nanowires 1,000 times thinner than a human hair and coated with antibodies, or proteins, that recognize circulating tumor cells. The device, the NanoVelcro Chip, works by “grabbing” circulating tumor cells, which break away from tumors and travel through the bloodstream, looking for places in the body to spread. Use of the chip in liquid biopsies could allow doctors to regularly and easily monitor cancer-related changes in patients, such as how well they’re responding to treatment. The research earned the lead investigators a place on the U.S. Cancer Moonshot program, an initiative led by former Vice President Joe Biden to make available more therapies to more patients and to prevent cancer. “It’s far better to draw a tube of blood once a month to monitor cancer than to make patients undergo repeated surgical procedures,” said Edwin Posadas, MD, medical director of the Urologic Oncology Program at Cedars-Sinai’s Samuel Oschin Comprehensive Cancer Institute and one of the lead investigators. “The power of this technology lies in its capacity to provide information that is equal to or even superior to traditional tumor sampling by invasive procedures.” Although some forms of prostate cancer are so slow-growing that they pose little risk to patients, other forms of the disease are lethal. Identifying which patients have which type of disease has become a crucial area of study because prostate cancer is one of the leading causes of cancer death among men in the U.S. Nearly 27,000 U.S. men are expected to die from the disease in 2017, according to the American Cancer Society. The research team has determined that in certain cancer cells, the nucleus is smaller than in other, more typical, cancer cells. Patients with the most advanced cases of aggressive prostate cancer have cells with these very small nuclei. The investigators’ teamwork also revealed that very small nuclei are associated with metastasis, or cancer spread, to the liver and lung in patients with advanced cases of prostate cancer. Those nuclei developed before the metastases were detected. Identifying very small nuclei early in the disease progression may help pinpoint which patients have high risk of developing cancer that can spread and be fatal. Hsian-Rong Tseng, PhD, professor, Department of Molecular and Medical Pharmacology in the David Geffen School of Medicine at UCLA and the other lead investigator, said that his work with Posadas is focused on improving the quality of life for cancer patients. “We’re on a mission to dramatically change patients’ everyday lives and their long-term outcomes,” Tseng said. “We now have powerful new tools to accomplish that.” Posadas and Tseng join an elite cadre of academicians, technology leaders and pharmaceutical experts as partners in the Blood Profiling Atlas in Cancer (BloodPAC) Project, a Moonshot program. Participants will collect and share data gathered from circulating tumor cells. Posadas and Tseng expect to contribute microscopic images from 1,000 circulating tumor cells that have not yet been analyzed, as well as additional data and cells they have cataloged. For the past five years, Posadas and Tseng have collected blood samples from cancer patients to profile and analyze the circulating tumor cells and other components. That process has helped them understand how prostate and other cancers evolve. The two investigators and their teams hope their findings will contribute to developing effective, targeted treatments for many types of cancer. “Minimally invasive methods to both diagnose and follow cancer, through simple blood tests, offer a unique and novel approach that can lead to earlier diagnosis and treatment, leading to more cures,” said Robert A. Figlin, MD, director of the Division of Hematology Oncology and deputy director of the Samuel Oschin Comprehensive Cancer Institute at Cedars- Sinai. About Cedars-Sinai Cedars-Sinai is a leader in providing high-quality healthcare encompassing primary care, specialized medicine and research. Since 1902, Cedars-Sinai has evolved to meet the needs of one of the most diverse regions in the nation, setting standards in quality and innovative patient care, research, teaching and community service. Today, Cedars-Sinai is known for its national leadership in transforming healthcare for the benefit of patients. Cedars-Sinai impacts the future of healthcare by developing new approaches to treatment and educating tomorrow’s health professionals. Additionally, Cedars-Sinai demonstrates a commitment to the community through programs that improve the health of its most vulnerable residents. About the David Geffen School of Medicine at UCLA Since opening in 1951, the David Geffen School of Medicine at UCLA has grown into an internationally recognized leader in research, medical education, patient care and public service. It has almost 2,000 full-time faculty members, including recipients of the Nobel Prize, the Pulitzer Prize and the National Medal of Science. More than 1,400 residents and fellows pursue advanced training at UCLA and its affiliated hospitals, which include Ronald Reagan UCLA Medical Center. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


News Article | December 5, 2016
Site: www.eurekalert.org

Researchers from the UCLA Department of Medicine, Division of Hematology Oncology and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have published two studies that define how key genetic factors affect blood-forming stem cells by either accelerating or hindering the cells' regenerative properties. The findings could one day lead to improved treatments for people undergoing common therapies for cancer such as chemotherapy and radiation. Blood-forming stem cells, or hematopoietic stem cells, are found in the bone marrow. These cells have two unique properties: They can self-renew and, through a process called differentiation, they can form any type of blood cell. A healthy immune system depends on the regenerative abilities of hematopoietic stem cells. Common cancer therapies such as chemotherapy and radiation can eliminate cancer by killing cancer cells. But these treatments also damage hematopoietic stem cells, which can impede the cells' ability to regenerate blood, slowing the immune system and resulting in a longer, more complicated recovery for people with cancer. Previous research indicated that certain genes may alter hematopoietic stem cells' regenerative capacity by either accelerating or hindering the cells' ability to restore the immune system, but more research was needed to pinpoint the specific genetic activity and effects. One of the new studies focused on a gene called Grb10 that is expressed by hematopoietic stem cells. Grb10's function was previously not known, so to better understand its role, the scientists deleted Grb10 from hematopoietic stem cells in lab dishes and in mice that had received radiation. They found that deleting Grb10 strongly promotes hematopoietic stem cell self-renewal and differentiation. In the other study, researchers analyzed a protein called DKK1. DKK1 is produced by a gene expressed by a specific "bone progenitor" cell that is present in the "niche," or cellular environment, that surrounds the hematopoietic stem cell. Typically, bone progenitor cells regenerate bone, but scientists had previously hypothesized that these cells also play an important role in regulating hematopoietic stem cells' ability to self-renew and differentiate into other blood cells. "The cellular niche is like the soil that surrounds the stem cell 'seed' and helps it grow and proliferate," said Dr. John Chute, professor of medicine in the Division of Hematology Oncology in the UCLA David Geffen School of Medicine and the study's senior author. "Our hypothesis was that the bone progenitor cell in the niche may promote hematopoietic stem cell regeneration after injury." The researchers showed that adding DKK1 to hematopoietic stem cells in lab dishes and mice that had received radiation produced a cascade effect within the cell niche that greatly enhanced hematopoietic stem cells' ability to self-renew and differentiate into other blood cells. Taken together, the studies uncover two molecular mechanisms that could potentially be manipulated to increase the regenerative properties of hematopoietic stem cells and improve cancer therapy. Scientists can now test drugs that inhibit Grb10 or test the effectiveness of administering DKK1 intravenously to promote immune regeneration in people who have received chemotherapy and radiation or those undergoing bone marrow transplants. Chute, who also is a member of the UCLA Jonsson Comprehensive Cancer Center, is the senior author of both papers. The first author of the Nature Medicine study is Heather Himburg and other authors are Mamle Quarmyne, Xiao Yan, Joshua Sasine, Liman Zhao, Grace Hancock, Jenny Kan, Katie Pohl and Evelyn Tran of UCLA; and Phuong Doan, Nelson Chao and Jeffrey Harris of Duke University. Other authors of the Cell Reports study are Yan, Himburg, Pohl, Quarmyne, Tran, Yurun Zhang, Tianchang Fang, Kan and Zhao of UCLA; and Doan and Chao of Duke University. The studies were published in the journals Nature Medicine (embargo lifts at 11:00 a.m. US Eastern time on Monday, December 5, 2016) and Cell Reports (published on November 1, 2016). The studies were funded by grants from the National Heart, Lung, and Blood Institute (HL-086998-05), the National Institute of Allergy and Infectious Diseases (AI-067798), a California Institute for Regenerative Medicine Leadership Award (LA1-08014), a National Institute of Allergy and Infectious Diseases' Centers for Medical Countermeasures Against Radiation Pilot Award (2U19AI067773-11), and by the UCLA Broad Stem Cell Research Center.


TORONTO and SAN DIEGO, Dec. 21, 2016 (GLOBE NEWSWIRE) -- Triphase Accelerator Corporation, a private drug development company dedicated to advancing novel compounds through Phase 2 proof-of-concept, today announced a new strategic collaboration with Celgene Corporation. Under the Agreement, Celgene has an option to acquire all Triphase Accelerator’s assets relating to TRPH-222 (CD22-4AP), an antibody-drug conjugate in development for lymphoma. Pursuant to the Agreement, Triphase Accelerator received an upfront payment from Celgene.  Triphase Accelerator will control development and will retain all commercial rights to TRPH-222 (CD22-4AP). If Celgene exercises its option to acquire TRPH-222 (CD22-4AP), Celgene will become responsible for development and commercialization, and Triphase Accelerator will be eligible to receive development, regulatory and sales milestone payments.  This is the third product option deal between Triphase Accelerator and Celgene. “This collaboration is important to Triphase Accelerator in multiple ways.  First, it continues to solidify the relationship we have developed over time with Celgene.  They have been a valued collaborator to us and we are grateful.  Just as importantly, it continues to validate our business model of acquiring early-stage assets and applying our methodology to accelerate programs through the proof-of-concept phase and into the clinic,” said Mohit Trikha, Ph.D., chief scientific officer, Head of Triphase Accelerator. “As we continue to acquire and develop new assets, we look forward to finding new ways to demonstrate how our approach is uniquely science based, efficient, and cost-effective, with the ultimate goal to help patients.” TRPH-222 is a novel, site-specific antibody-drug conjugate (ADC) targeting CD22, a B-cell-restricted sialogycoprotein that is an important modulator of B-cell signaling and survival, which is expressed on nearly all B-cell malignancies.  CD22 is a validated ADC target for Non-Hodgkin’s lymphoma and acute lymphoid leukemia.  The compound itself combines a site-specific modified humanized antibody conjugated to a toxin payload and a 4AP linker. “We have enjoyed a long-standing relationship with Triphase Accelerator and believe in their approach to drug development,” said Celgene’s President of Hematology Oncology, Michael Pehl. “This latest agreement, which closely follows our acquisition of their marizomib asset, represents our confidence in their approach to drug development, and we look forward to a continued collaboration with the company.” About Triphase Accelerator Triphase Accelerator is a private drug development company with a primary focus on oncology and with operations in Toronto and San Diego. Triphase Accelerator is dedicated to advancing novel compounds through Phase 2 proof-of-concept clinical studies using a unique, science-based, high-quality model that is faster and more cost-effective than traditional pharmaceutical and biotech industry drug development approaches. Triphase Accelerator was spun out of the Ontario Institute for Cancer Research (OICR), with support from the Fight Against Cancer Innovation Trust (FACIT), MaRS Innovation and MaRS. It has a strategic relationship with Celgene for oncology-focused drug development opportunities. For more information, visit www.triphaseco.com or LinkedIn.


News Article | February 15, 2017
Site: www.eurekalert.org

LOS ANGELES (Feb. 13, 2017) - A team of investigators from Cedars-Sinai and UCLA is using a new blood-analysis technique and tiny experimental device to help physicians predict which cancers are likely to spread by identifying and characterizing tumor cells circulating through the blood. The investigators are conducting "liquid biopsies" by running blood through a postage-stamp-sized chip with nanowires 1,000 times thinner than a human hair and coated with antibodies, or proteins, that recognize circulating tumor cells. The device, the NanoVelcro Chip, works by "grabbing" circulating tumor cells, which break away from tumors and travel through the bloodstream, looking for places in the body to spread. Use of the chip in liquid biopsies could allow doctors to regularly and easily monitor cancer-related changes in patients, such as how well they're responding to treatment. The research earned the lead investigators a place on the U.S. Cancer Moonshot program, an initiative led by former Vice President Joe Biden to make available more therapies to more patients and to prevent cancer. "It's far better to draw a tube of blood once a month to monitor cancer than to make patients undergo repeated surgical procedures," said Edwin Posadas, MD, medical director of the Urologic Oncology Program at Cedars-Sinai's Samuel Oschin Comprehensive Cancer Institute and one of the lead investigators. "The power of this technology lies in its capacity to provide information that is equal to or even superior to traditional tumor sampling by invasive procedures." Although some forms of prostate cancer are so slow-growing that they pose little risk to patients, other forms of the disease are lethal. Identifying which patients have which type of disease has become a crucial area of study because prostate cancer is one of the leading causes of cancer death among men in the U.S. Nearly 27,000 U.S. men are expected to die from the disease in 2017, according to the American Cancer Society. The research team has determined that in certain cancer cells, the nucleus is smaller than in other, more typical, cancer cells. Patients with the most advanced cases of aggressive prostate cancer have cells with these very small nuclei. The investigators' teamwork also revealed that very small nuclei are associated with metastasis, or cancer spread, to the liver and lung in patients with advanced cases of prostate cancer. Those nuclei developed before the metastases were detected. Identifying very small nuclei early in the disease progression may help pinpoint which patients have high risk of developing cancer that can spread and be fatal. Hsian-Rong Tseng, PhD, professor, Department of Molecular and Medical Pharmacology in the David Geffen School of Medicine at UCLA and the other lead investigator, said that his work with Posadas is focused on improving the quality of life for cancer patients. "We're on a mission to dramatically change patients' everyday lives and their long-term outcomes," Tseng said. "We now have powerful new tools to accomplish that." Posadas and Tseng join an elite cadre of academicians, technology leaders and pharmaceutical experts as partners in the Blood Profiling Atlas in Cancer (BloodPAC) Project, a Moonshot program. Participants will collect and share data gathered from circulating tumor cells. Posadas and Tseng expect to contribute microscopic images from 1,000 circulating tumor cells that have not yet been analyzed, as well as additional data and cells they have cataloged. For the past five years, Posadas and Tseng have collected blood samples from cancer patients to profile and analyze the circulating tumor cells and other components. That process has helped them understand how prostate and other cancers evolve. The two investigators and their teams hope their findings will contribute to developing effective, targeted treatments for many types of cancer. "Minimally invasive methods to both diagnose and follow cancer, through simple blood tests, offer a unique and novel approach that can lead to earlier diagnosis and treatment, leading to more cures," said Robert A. Figlin, MD, director of the Division of Hematology Oncology and deputy director of the Samuel Oschin Comprehensive Cancer Institute at Cedars- Sinai. Cedars-Sinai is a leader in providing high-quality healthcare encompassing primary care, specialized medicine and research. Since 1902, Cedars-Sinai has evolved to meet the needs of one of the most diverse regions in the nation, setting standards in quality and innovative patient care, research, teaching and community service. Today, Cedars-Sinai is known for its national leadership in transforming healthcare for the benefit of patients. Cedars-Sinai impacts the future of healthcare by developing new approaches to treatment and educating tomorrow's health professionals. Additionally, Cedars-Sinai demonstrates a commitment to the community through programs that improve the health of its most vulnerable residents. Since opening in 1951, the David Geffen School of Medicine at UCLA has grown into an internationally recognized leader in research, medical education, patient care and public service. It has almost 2,000 full-time faculty members, including recipients of the Nobel Prize, the Pulitzer Prize and the National Medal of Science. More than 1,400 residents and fellows pursue advanced training at UCLA and its affiliated hospitals, which include Ronald Reagan UCLA Medical Center.


News Article | February 14, 2017
Site: www.cemag.us

A team of investigators from Cedars-Sinai and UCLA is using a new blood-analysis technique and tiny experimental device to help physicians predict which cancers are likely to spread by identifying and characterizing tumor cells circulating through the blood. The investigators are conducting "liquid biopsies" by running blood through a postage-stamp-sized chip with nanowires 1,000 times thinner than a human hair and coated with antibodies, or proteins, that recognize circulating tumor cells. The device, the NanoVelcro Chip, works by "grabbing" circulating tumor cells, which break away from tumors and travel through the bloodstream, looking for places in the body to spread. Use of the chip in liquid biopsies could allow doctors to regularly and easily monitor cancer-related changes in patients, such as how well they're responding to treatment. The research earned the lead investigators a place in the U.S. Cancer Moonshot program, an initiative led by former Vice President Joe Biden to make more therapies available to more patients and to prevent cancer. "It's far better to draw a tube of blood once a month to monitor cancer than to make patients undergo repeated surgical procedures," says Edwin Posadas, MD, medical director of the Urologic Oncology Program at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute and one of the lead investigators. "The power of this technology lies in its capacity to provide information that is equal to or even superior to traditional tumor sampling by invasive procedures." Although some forms of prostate cancer grow so slowly that they pose little risk to patients, other forms of the disease are lethal. Identifying which patients have which type of disease has become a crucial area of study because prostate cancer is one of the leading causes of cancer death among men in the U.S. Nearly 27,000 U.S. men are expected to die from the disease in 2017, according to the American Cancer Society. The research team has determined that in certain cancer cells, the nucleus is smaller than in other, more typical, cancer cells. Patients with the most advanced cases of aggressive prostate cancer have cells with these very small nuclei. The investigators' teamwork also revealed that very small nuclei are associated with metastasis, or cancer spread, to the liver and lung in patients with advanced cases of prostate cancer. Those nuclei developed before the metastases were detected. Identifying very small nuclei early in the disease progression may help pinpoint which patients have high risk of developing cancer that can spread and be fatal. Hsian-Rong Tseng, PhD, professor, Department of Molecular and Medical Pharmacology in the David Geffen School of Medicine at UCLA and the other lead investigator, says his work with Posadas is focused on improving the quality of life for cancer patients. "We're on a mission to dramatically change patients' everyday lives and their long-term outcomes," Tseng says. "We now have powerful new tools to accomplish that." Posadas and Tseng join an elite cadre of academicians, technology leaders and pharmaceutical experts as partners in the Blood Profiling Atlas in Cancer (BloodPAC) Project, a Moonshot program. Participants will collect and share data gathered from circulating tumor cells. Posadas and Tseng expect to contribute microscopic images from 1,000 circulating tumor cells that have not yet been analyzed, as well as additional data and cells they have cataloged. For the past five years, Posadas and Tseng have collected blood samples from cancer patients to profile and analyze the circulating tumor cells and other components. That process has helped them understand how prostate and other cancers evolve. The two investigators and their teams hope their findings will contribute to developing effective, targeted treatments for many types of cancer. "Minimally invasive methods to both diagnose and follow cancer, through simple blood tests, offer a unique and novel approach that can lead to earlier diagnosis and treatment, leading to more cures," says Robert A. Figlin, MD, director of the Division of Hematology Oncology and deputy director of the Samuel Oschin Comprehensive Cancer Institute.


Marizomib is a novel brain-penetrant proteasome inhibitor in development for patients with glioblastoma and relapsed and/or refractory multiple myeloma. TORONTO and SAN DIEGO, Nov. 17, 2016 (GLOBE NEWSWIRE) -- Triphase Accelerator Corporation, a private drug development company dedicated to advancing novel compounds through Phase 2 proof-of-concept, today announced that Celgene Corporation, through an affiliate, has acquired the company’s assets related to its proteasome inhibitor, marizomib (MRZ), which is in development for glioblastoma and relapsed and/or refractory multiple myeloma. Under the terms of the agreement, Celgene will make an upfront payment plus additional regulatory, approval and sales milestone payments.  Specific financial terms were not disclosed.  “This acquisition validates the potential of marizomib based on early clinical results.  Our vision is to become a leading early stage oncology drug development company, and this first opt-in by Celgene brings us a step closer to achieving that goal,” said Mohit Trikha, Ph.D., chief scientific officer, Triphase Accelerator Corporation. “Just as importantly, this transaction affords us the opportunity to accelerate our efforts on advancing other assets in our pipeline.” “Consistent with our deep commitment and passion for the patients, glioblastoma is an area of significant unmet medical need, and Celgene is committed to helping these patients.  We are pleased with Triphase Accelerator’s rapid and high quality work to date, and we value the exceptional collaboration we have with them to advance marizomib,” said Celgene’s President of Hematology Oncology, Michael Pehl. Going forward Celgene has full responsibility for the development of marizomib and will pay Triphase to complete the ongoing clinical studies with marizomib, including a Phase 1 study in relapsed refractory multiple myeloma, a Phase 2 study in recurrent glioma and a Phase 1 study in newly diagnosed glioma. About Marizomib Marizomib is a novel, brain-penetrant proteasome inhibitor, which inhibits all three proteasome subunits.  Triphase Accelerator is developing marizomib in both intravenous (IV) and oral formulations as a proteasome inhibitor for hematologic malignancies and solid tumors. The IV formulation has been evaluated in more than 300 patients in multiple clinical studies in patients with solid and hematologic malignancies, either as a single agent or in combination with dexamethasone, a histone deacetylase inhibitor, or an immunomodulatory drug. The company is currently evaluating marizomib in a proof-of-concept clinical study in combination with bevacizumab (Avastin®) in patients with Grade IV malignant glioma (glioblastoma), and has received Orphan Drug designation for marizomib in glioblastoma in the United States from the FDA. In addition, Triphase Accelerator is currently developing marizomib in combination with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, and has received Orphan Drug designation for marizomib in multiple myeloma in the United States and the European Union. Triphase Accelerator is also evaluating an oral formulation in preclinical studies. Marizomib has not been approved for any use in any country. About Triphase Accelerator Triphase Accelerator is a private drug development company with a primary focus on oncology and with operations in Toronto and San Diego. Triphase Accelerator is dedicated to advancing novel compounds through Phase 2 proof-of-concept clinical studies using a unique, science-based, high-quality model that is faster and more cost-effective than traditional pharmaceutical and biotech industry drug development approaches. Triphase Accelerator was spun out of the Ontario Institute for Cancer Research (OICR), with support from the Fight Against Cancer Innovation Trust (FACIT), MaRS Innovation and MaRS. It has a strategic relationship with Celgene for marizomib. For more information, visit www.triphaseco.com or LinkedIn.


News Article | December 6, 2016
Site: www.businesswire.com

SAN DIEGO--(BUSINESS WIRE)--bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, provided updates across its hematopoietic stem cell (HSC) gene therapy programs, including: “Our focus is learning, adjusting and implementing to innovate on behalf of the patients we aim to serve. This year we have made tremendous progress against this objective,” said Nick Leschly, chief bluebird. “In 2016, we focused on further enhancing our LentiGlobin programs in TDT and SCD by implementing high potential manufacturing and protocol amendments while advancing our lead bb2121 oncology program and commercialization capabilities. We are encouraged by the data presented at ASH and how that has informed our plans for 2017.” TDT Program Updates The company announced that the first patient has been enrolled in Northstar-2 (HGB-207), a Phase 3, global, multi-center study in patients with TDT with non-β0/β0 genotypes. This study uses LentiGlobin drug product manufactured with updated processes using transduction enhancers. LentiGlobin DP VCN for the first patient to be treated in Northstar-2 is 2.9 vector copies per diploid genome (c/dg), with 77% of the stem cells lentiviral vector positive (LVV+). Interim data from the Northstar study were highlighted today in an oral presentation by Alexis Thompson, M.D., M.P.H., head of the hematology section of the Division of Hematology Oncology Transplantation and Director of the Comprehensive Thalassemia Program at the Ann and Robert H. Lurie Children’s Hospital of Chicago, where she also serves as the A. Watson and Sarah Armour Endowed Chair for Childhood Cancer and Blood Disorders. LentiGlobin Gene Therapy for Transfusion-Dependent β-Thalassemia: Update from the Northstar (HGB-204) Phase 1/2 Clinical Study (Abstract #1175) The Northstar Study is an ongoing, open-label, single-dose, international, multicenter Phase 1/2 study designed to evaluate the safety and efficacy of LentiGlobin drug product for the treatment of subjects with TDT. Results as of September 16, 2016 include: “The maturing interim data from the Northstar study support the potential for LentiGlobin to provide a transformative treatment option for patients with TDT by reducing or eliminating the burdensome cycle of chronic blood transfusions and iron chelation,” said David Davidson, chief medical officer, bluebird bio. “In addition, we are pleased by the robust vector copy number and high proportion of LVV+ CD34+ stem cells in the drug product manufactured using transduction enhancers for the first patient to be treated in the Phase 3 Northstar-2 study. If the clinical correlation between drug product VCN and hemoglobin production observed in the Northstar study continues with drug product manufactured utilizing process 2, we are hopeful that LentiGlobin drug product with higher VCNs will consistently yield clinically meaningful outcomes for patients with TDT across all genotypes.” Severe Sickle Cell Disease Program Updates bluebird bio has amended the protocol of the ongoing HGB-206 study in patients with severe SCD to incorporate several changes with the goal of increasing production of HbAT87Q, such as increasing the percentage of transduced cells through manufacturing improvements, increasing target busulfan area under the curve (AUC), introducing a minimum period of regular blood transfusions prior to stem cell collection and exploring an alternate hematopoietic stem cell procurement method with the goal of increasing transduced cell dose. Enrollment has begun under this modified protocol, and the DP VCN for the first patient enrolled under the new protocol was 3.3 c/dg, with 83% of the stem cells LVV+, with infusion planned for early 2017. Interim data from the HGB-206 study were highlighted today in an oral presentation by Julie Kanter, M.D., Medical University of South Carolina, Charleston, SC. Interim Results from a Phase 1/2 Clinical Study of LentiGlobin™ Gene Therapy for Severe Sickle Cell Disease (Abstract #1176) HGB-206 is an ongoing, open-label study designed to evaluate the safety and efficacy of LentiGlobin drug product in the treatment of subjects with severe SCD. Results, as of November 9, 2016, include: Cerebral Adrenoleukodystrophy Program Updates bluebird bio also announced plans to expand enrollment by up to eight additional patients in the ongoing Starbeam Phase 2/3 clinical study of Lenti-D drug product in patients less than 18 years of age with cerebral adrenoleukodystrophy (CALD). The expansion of the study is intended to enable the first manufacture of Lenti-D in Europe and subsequent treatment of subjects in Europe, and to bolster the overall clinical data package for potential future regulatory filings in the United States and Europe. bluebird bio plans to begin treating additional patients in the Starbeam study in early 2017. bluebird bio will host a live webcast at 8:30 p.m. PT (11:30 p.m. ET) today, December 5, 2016. The live webcast can be accessed under "Calendar of Events" in the Investors and Media section of the company's website at www.bluebirdbio.com. Transfusion-dependent β-thalassemia (TDT), also called β-thalassemia major or Cooley’s anemia, is an inherited blood disease that can cause severe anemia and can be fatal within the first few years of life if not treated. TDT is one of the most common genetic diseases in the world, and approximately 60,000 children are born every year with a serious form of the disease. Despite advances in the supportive conventional management of the disease, which consists of frequent and lifelong blood transfusions and iron chelation therapy, there is still a significant unmet medical need, including the risk for significant morbidity and early mortality. Currently, the only advanced treatment option for transfusion-dependent β-thalassemia is allogeneic hematopoietic stem cell transplant (HSCT). Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, graft vs. host disease (GvHD) and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT. Sickle cell disease (SCD) is an inherited disease caused by a mutation in the beta-globin gene that results in sickle-shaped red blood cells. The disease is characterized by anemia, vaso-occlusive crisis, infections, stroke, overall poor quality of life and sometimes, early death. Where adequate medical care is available, common treatments for patients with SCD largely revolve around management and prevention of acute sickling episodes. Chronic management may include hydroxyurea and, in certain cases, chronic transfusions. Given the limitations of these treatments, there is no effective long-term treatment. The only advanced treatment for SCD is allogeneic HSCT. Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, GvHD and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT. The Phase 2/3 Starbeam Study is assessing the efficacy and safety of Lenti-D, an investigational gene therapy, in boys up to 17 years of age with CALD. The study involves transplantation with a patient’s own stem cells, which are modified to contain a functioning copy of the ABCD1 gene. This gene addition should result in the production of functional adrenoleukodystrophy protein (ALDP), a protein critical for the breakdown of very long chain fatty acids (VLCFAs). Buildup of VLCFAs in the central nervous system contributes to neurodegeneration in CALD. Patients enrolled in the study are: The primary efficacy endpoint for the Starbeam study is the proportion of subjects who are alive and have none of six major functional disabilities (MFDs) at 24 months post treatment. MFDs are six symptoms captured in the Neurologic Function Score (NFS) that, if present, are expected to severely affect the patient’s capacity for independent living: loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, and complete loss of voluntary movement. Cerebral adrenoleukodystrophy (CALD) is a rare and commonly fatal, X-linked, genetic, neurodegenerative disease that primarily affects young boys. CALD involves a progressive destruction of myelin, the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control. Symptoms usually occur in early childhood and progress rapidly if untreated, leading to severe loss of neurological function and eventual death within 2-5 years in most patients. Early diagnosis is critical for boys to receive effective treatment. The worldwide incidence rate for ALD is approximately one in 21,000 male newborns; of those, 30-40% are affected by the cerebral form of the disease. Currently, the only effective treatment option for patients with CALD is allogeneic HSCT. Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, GvHD and opportunistic infections, particularly in patients who undergo non-sibling-matched allogeneic HSCT. With its lentiviral-based gene therapies, T cell immunotherapy expertise and gene editing capabilities, bluebird bio has built an integrated product platform with broad potential application to severe genetic diseases and cancer. bluebird bio’s gene therapy clinical programs include its Lenti-D™ product candidate, currently in a Phase 2/3 study, called the Starbeam Study, for the treatment of cerebral adrenoleukodystrophy, and its LentiGlobin™ BB305 product candidate, currently in four clinical studies for the treatment of transfusion-dependent β-thalassemia and severe sickle cell disease. bluebird bio’s oncology pipeline is built upon the company’s leadership in lentiviral gene delivery and T cell engineering, with a focus on developing novel T cell-based immunotherapies, including chimeric antigen receptor (CAR T) and T cell receptor (TCR) therapies. bluebird bio’s lead oncology program, bb2121, is an anti-BCMA CAR T program partnered with Celgene. bb2121 is currently being studied in a Phase 1 trial for the treatment of relapsed/refractory multiple myeloma. bluebird bio also has discovery research programs utilizing megaTALs/homing endonuclease gene editing technologies with the potential for use across the company’s pipeline. Forward-Looking Statements This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company’s research, development, manufacturing and regulatory approval plans for its LentiGlobin product candidate to treat transfusion-dependent ß-thalassemia and severe sickle cell disease and its Lenti-D product candidate to treat cerebral adrenoleukodystrophy, including statements whether the manufacturing process changes for LentiGlobin will improve outcomes of patients with transfusion-dependent ß-thalassemia and severe sickle cell disease, whether the planned changes to the HGB-206 clinical trial protocol will improve outcomes in patients with severe sickle cell disease. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks that the preliminary positive efficacy and safety results from our prior and ongoing clinical trials of LentiGlobin and Lenti-D will not continue or be repeated in our ongoing, planned or expanded clinical trials of LentiGlobin or the ongoing expanded clinical trial of Lenti-D, the risks that the changes we have made in the LentiGlobin manufacturing process or the HGB-206 clinical trial protocol will not result in improved patient outcomes, risks that the current or planned clinical trials of LentiGlobin and Lenti-D will be insufficient to support regulatory submissions or marketing approval in the US and EU, the risk of a delay in the enrollment of patients in our clinical studies, and the risk that any one or more of our product candidates will not be successfully developed, approved or commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in our most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and bluebird bio undertakes no duty to update this information unless required by law.


News Article | February 28, 2017
Site: www.eurekalert.org

CINCINNATI--Researchers at the University of Cincinnati (UC) College of Medicine have discovered a new potential strategy to personalize therapy for brain and blood cancers. These findings are reported in the Feb. 28 edition of Cell Reports. "We found a new combination of therapeutics that could treat cancers that lack a protein called PTEN. PTEN is an important tumor suppressor, which means that it stops cell growth and division according to the needs of the body," says David Plas, PhD, Anna and Harold W. Huffman Endowed Chair for Glioblastoma Experimental Therapeutics. Plas is an associate professor in the Department of Cancer Biology, a member of the University of Cincinnati Cancer Institute and a researcher in the Brain Tumor Center of the UC Gardner Neuroscience Institute. Atsuo Sasaki, PhD, and Hala Elnakat Thomas, PhD, both in the Division of Hematology Oncology at the UC College of Medicine, were collaborators on the study. In early work using experimental therapeutics in human cancer cells and in tumor models, the Plas laboratory showed that stopping the production and function of the protein S6K1 could eliminate PTEN-deficient glioblastoma cells. Glioblastoma, the most aggressive form of brain cancer, is difficult to treat with targeted therapeutics. "We used support from the Huffman Foundation to conduct a sophisticated biochemical analysis of how cells respond to S6K1 targeting," Plas says. "Combining the biochemical results with computational analysis gave us the insight that we needed--there are targets in addition to S6K1 that can be hit to trigger the elimination of PTEN-deficient cancer cells." With the new information, the research team tested pharmaceutical-grade drug combinations for the ability to eliminate PTEN-deficient cancer cells. Results showed that the drugs LY-2779964 and BMS-777607 work together to specifically eliminate PTEN-deficient cells. "This is a completely new combination of targets in oncology," Plas says. "We have great hope that our new data will lead academic and industry researchers to investigate S6K1 as the center of new combination strategies for cancers of the brain, blood and other tissues." Future work in the project will test the safety and efficacy of the new combination using tumor models, with the goal of preparing the combination strategy for clinical trial. Ronald Warnick, MD, medical director of the UC Brain Tumor Center and a professor in the Department of Neurosurgery within the UC College of Medicine, adds that this kind of project is necessary in finding new and beneficial therapies for brain tumors. "There is a desperate need for novel therapeutic agents for patients with glioblastoma," he says. "This combination of drugs has the potential to become a game-changer." This study was funded by the American Cancer Society, the National Institutes of Health (R01 CA133164, R01 CA168815, R21NS100077, R01NS089815), the UC Brain Tumor Center, the Anna and Harold W. Huffman Endowed Chair for Glioblastoma Experimental Therapeutics and the UC Medical Scientist Training Program. Plas cites no conflict of interest.

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