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The team of investigators immunized a macaque with a special cocktail of engineered proteins mimicking the surface glycoproteins of ebolaviruses to induce broadly protective responses.  The scientists then screened immune cells of the vaccinated animal to specifically isolate those monoclonal antibodies that reacted to multiple ebolaviruses.  After searching through millions of immune cells, a cross-reactive antibody (CA45) was isolated that was able to neutralize cellular infection by all pathogenic ebolaviruses. CA45, when given to already infected rodents at the peak of their disease, was able to protect the animals from the otherwise lethal infection.  The scientists then combined CA45 with another antibody they discovered previously and demonstrated that the combination showed superior activity, protecting mice, guinea pigs and ferrets from infections with Ebola, Sudan, and Bundibugyo viruses with almost no sign of disease. This is the first time a therapeutic agent has been able to fully protect animals against all three pathogenic ebolaviruses. The glycoprotein (GP) on the surface of the ebolavirus is responsible for entry into the cells.  The entry process involves first interaction with the cell surface followed by transport to specialized cellular compartments called endosomes where GP interacts with its cellular receptor.  Finally the GP mediates the last step of entry, the fusion of the viral and endosomal membrane that allows the virus to release its content into the cells.  Using a variety of methods the team identified the specific region of ebolavirus GP that is attacked by CA45.  This region is within the so-called fusion loop that mediates fusion of the viral and endosomal membrane.  The site attacked by CA45 has a remarkably similar structure in the GP of various ebolaviruses, explaining its ability to cross protect against multiple viruses.  Recently similar broadly neutralizing antibodies targeting the fusion domain of HIV and influenza have been discovered indicating that this region is a key site of vulnerability for these viruses. The fact that such a broadly protective antibody was elicited by immunization with an engineered vaccine suggests the feasibility of developing a vaccine protective against multiple ebolaviruses.  "With every new antibody we learn a little more about this virus and how it can be attacked," says Dr. M. Javad Aman of Integrated BioTherapeutics and a senior author on the paper.  He went on to say "We are carefully analyzing this information to devise strategies to make a single vaccine effective against all ebolaviruses-- such a vaccine may be entirely within reach now." "We are on our way to designing novel vaccines and immunotherapeutics for broader protection against all pathogenic ebolaviruses, with the insights we have been gaining," says Dr. Yuxing Li, Associate Professor of IBBR and the co-corresponding author of the paper. The paper is titled "Immunization-elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability." In addition to Drs. Li and Aman and the co-first authors Drs. Xuelian Zhao and Katie A. Howell, contributors include Shihua He, Jennifer M. Brannan, Anna Z. Wec, Edgar Davidson, Hannah L. Turner, Chi-I Chiang, Lin Lei, J. Maximilian Fels, Hong Vu, Sergey Shulenin, Ashley N. Turonis, Ana I. Kuehne, Guodong Liu, Mi Ta, Yimeng Wang, Christopher Sundling, Yongli Xiao, Jennifer S. Spence, Benjamin J. Doranz, Frederick W. Holtsberg, Andrew B. Ward, Kartik Chandran, John M. Dye, and Xiangguo Qiu. This work was supported by a contract (HDTRA1-13-C-0015) from US Defense Threat Reduction Agency (DTRA) and NIAID/NIH grants R43AI124765, R01AI126587, U19AI109762, Intramural Research Award from IBBR, University of Maryland, NIAID contract HHSN272201400058C, JSTO-DTRA project CB4077, and also partially supported by Public Health Agency of Canada (PHAC). IBT is a biotechnology company focused on the discovery of novel vaccines and therapies for emerging infectious diseases with a pipeline that includes promising product candidates for bacterial and viral infections including unique pan-filovirus immunotherapeutics and vaccines, vaccines for Staphylococcal infections, and a variety of other product candidates for emerging viruses.  Located in Rockville, MD, IBT has a close working relationship with United States Government agencies including the National Institute of Allergy and Infectious Diseases (NIAID/NIH). National Cancer Research Institute (NCI), Department of Defense (DOD), United States Army Medical Research Institute of Infection Diseases (USAMRIID) as well as many biotechnology and pharmaceutical companies and academic laboratories.  For more information, visit www.integratedbiotherapeutics.com. About the Institute for Bioscience and Biotechnology Research (IBBR) IBBR is a University System of Maryland joint research enterprise among the University of Maryland College Park, the University of Maryland Baltimore, and the National Institute of Standards and Technology.  With a long-standing scientific focus on structure-function relationships of biomolecules, genetic systems, and applications, e.g., vaccines, therapeutics, drug delivery technologies, and biomanufacturing, IBBR's mission is to leverage its unique capabilities and infrastructure to marshal innovative technologies and expertise across its partnering institutions, to foster integrated, cross-disciplinary team approaches to scientific research and education, and to pursue translational programs and projects aimed at advancing innovations to commercialization in real world applications. The Institute also serves to expand the economic base of science and technology in the state of Maryland and at the national level. For more information visit http://www.ibbr.umd.edu/ USAMRIID's mission is to provide leading edge medical capabilities to deter and defend against current and emerging biological threat agents. Research conducted at USAMRIID leads to medical solutions-vaccines, drugs, diagnostics, and information-that benefit both military personnel and civilians. The Institute plays a key role as the lead military medical research laboratory for the Defense Threat Reduction Agency's Joint Science and Technology Office for Chemical and Biological Defense. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command. For more information, visit www.usamriid.army.mil Albert Einstein College of Medicine is one of the nation's premier centers for research, medical education and clinical investigation. During the 2016-2017 academic year, Einstein is home to 717 M.D. students, 166 Ph.D. students, 103 students in the combined M.D./Ph.D. program, and 278 postdoctoral research fellows. The College of Medicine has more than 1,900 full-time faculty members located on the main campus and at its clinical affiliates. In 2016, Einstein received more than $160 million in awards from the National Institutes of Health (NIH). This includes the funding of major research centers at Einstein in aging, intellectual development disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States through Montefiore and an affiliation network involving hospitals and medical centers in the Bronx, Brooklyn and on Long Island. For more information, please visit www.einstein.yu.edu. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/immunization-elicited-antibody-shows-universal-protection-against-multiple-ebolaviruses-300459398.html


News Article | May 15, 2017
Site: www.businesswire.com

PRINCETON, N.J.--(BUSINESS WIRE)--UPDATED — Advaxis, Inc. (NASDAQ:ADXS), a biotechnology company developing cancer immunotherapies, today published online a poster previously presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool that showed axalimogene filolisbac achieved durable response in a patient with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC). Sharad Ghamande, MD, principal investigator and Professor and Director of Gynecologic Oncology at the Georgia Cancer Center at Augusta University, discussed cervical cancer and axalimogene filolisbac in detail recently on the JENNIE Show on the News Channel ABC 6, WJBF in Augusta, GA. Also, one patient in this phase 1 study experienced an ongoing and durable partial response, and this patient was recently featured in the Augusta Chronicle, as she is being treated by Dr. Ghamande at the Georgia Cancer Center at Augusta University. Read the full Augusta Chronicle article here. Overall, nine patients who had documented disease progression after they had received curative treatments of chemotherapy and/or radiation with or without bevacizumab were enrolled in this phase 1, open-label, dose-determining study. Axalimogene filolisbac was well-tolerated across two dose levels. The study also established a recommended phase 2 dose of 1×1010 CFU and demonstrated antitumor activity at that dose. Axalimogene filolisbac was safely administered at 5 and 10 times the dose levels previously studied, without significant toxicity. “ The best overall tumor response in eight of the nine enrolled patients is encouraging in evaluating the potential of axalimogene filolisbac,” said Dr. Ghamande. “ We were pleased to see a sustained and durable partial response in one patient, which is very rare for this kind of tumor that is unresponsive to chemotherapy, and survival in these patients is often less than 10 months. In addition, we could safely administer the drug at 5 and 10 times the dose levels previously studied, without any significant toxicity.” There was only one instance of dose-limiting toxicity, with that patient experiencing a grade 3 treatment related adverse event (TRAE) of hypotension at a dose of 5×109 CFU. Across all doses, eight of nine patients experienced a grade 1-2 TRAE, including chills, nausea and hypotension. The poster on the phase 1 data, “ High-dose treatment with ADXS11-001, a Listeria monocytogenes-listeriolysin O (Lm-LLO) immunotherapy, in women with cervical cancer: a phase I, dose-escalation study” (no. 58) is available at www.advaxis.com. The company is preparing to initiate a phase 3 trial in PRmCC later this year. Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack. In a phase 2 trial evaluating axalimogene filolisbac for the treatment of persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC), the drug candidate showed a 12-month overall survival rate of 38 percent observed in 50 patients in the trial. This is a 52 percent improvement over the 12-month overall survival rate that was expected in the trial’s patient population based on prognostic factors. Axalimogene filolisbac has received Fast Track designation for adjuvant therapy for high-risk locally advanced cervical cancer (HRLACC) and a Special Protocol Assessment for the Phase 3 AIM2CERV trial in HRLACC patients. The immunotherapy has also received orphan drug designation in three clinical indications. Located in Princeton, N.J., Advaxis, Inc. is a biotechnology company developing multiple cancer immunotherapies based on its proprietary Lm Technology™. The Lm Technology, using bioengineered live attenuated Listeria monocytogenes (Lm) bacteria, is the only known cancer immunotherapy agent shown in preclinical studies to both generate cancer fighting T cells directed against cancer antigens and neutralize Tregs and myeloid-derived suppressor cells (MDSCs) that protect the tumor microenvironment from immunologic attack and contribute to tumor growth. Advaxis' lead Lm Technology immunotherapy, axalimogene filolisbac, targets HPV-associated cancers and is in clinical trials for three potential indications: Phase 3 in invasive cervical cancer, Phase 2 in head and neck cancer, and Phase 2 in anal cancer. The FDA has granted axalimogene filolisbac orphan drug designation for each of these three clinical settings, as well as Fast Track designation for adjuvant therapy for HRLACC patients and a SPA for the Phase 3 AIM2CERV trial in HRLACC patients. Axalimogene filolisbac has also been classified as an advanced therapy medicinal product for the treatment of cervical cancer by the EMA’s CAT. Advaxis has two additional immunotherapy products: ADXS-PSA in prostate cancer and ADXS-HER2 in HER2 expressing solid tumors, in human clinical development. In addition, Advaxis and Amgen are developing ADXS-NEO, an investigational cancer immunotherapy treatment designed to activate a patient's immune system to respond against the unique mutations, or neoepitopes, contained in and identified from each individual patient's tumor, with plans to commence a Phase 1 clinical trial in 2017. To learn more about Advaxis, visit www.advaxis.com and connect on Twitter, LinkedIn, Facebook, and YouTube. This press release contains forward-looking statements, including, but not limited to, statements regarding Advaxis’ ability to develop the next generation of cancer immunotherapies, and the safety and efficacy of Advaxis’ proprietary immunotherapy, axalimogene filolisbac. These forward-looking statements are subject to a number of risks including the risk factors set forth from time to time in Advaxis’ SEC filings including, but not limited to, its report on Form 10-K for the fiscal year ended October 31, 2016, which is available at http://www.sec.gov. Any forward-looking statements set forth in this presentation speak only as of the date of this presentation. We do not intend to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof other than as required by law. You are cautioned not to place undue reliance on any forward-looking statements.


News Article | November 9, 2016
Site: www.sciencedaily.com

Tagging gold nanoparticles with a small dose of radiation has helped researchers trace the precious metal as it delivers a drug right into the heart of cancer cells, according to new laboratory research being presented at the 2016 National Cancer Research Institute (NCRI) Cancer conference. Researchers from the CRUK/MRC Oxford Institute for Radiation Oncology have been working on better ways to transport a drug directly into the control room of cancer cells, where the chromosomes are kept. This specific drug targets a molecule -- telomerase -- that builds up the protective caps at the end of chromosomes called telomeres. In most cells of the body, telomeres act like an in-built timer to ensure that the cell does not live past its expiry date. Telomeres shorten each time the cell divides. Once a critical length is reached, the cell can no longer divide and it dies. Cancer cells manage to get around this safety check by reactivating telomerase allowing them to continue to grow out of control. One of the biggest hurdles in treating cancer is getting effective drugs into cancer cells, particularly to where the chromosomes are stored. Gold nanoparticles have proven to be well suited to being absorbed into cells, safely delivering drugs that could otherwise be blocked. By engineering the gold nanoparticles and adding the radioactive tracer, the researchers were able to prove that their drug was reaching the desired target in skin cancer cells grown in the lab and was shutting telomerase down, halting cancer's growth. While the radioactive tracer was used to precisely follow the drug in this study, the same method can also be used to deliver a dose of radioactivity to cancer cells, helping to kill them. This second dose is especially powerful because inactivation of telomerase makes cancer cells more sensitive to radiation. Professor Kate Vallis, lead researcher based at the CRUK/MRC Oxford Institute for Radiation Oncology, said: "Gold is precious in more than one way. We have used tiny gold nanoparticles loaded with targeted drugs to kill cancer cells in the laboratory. Our long term goal is to design new treatments for cancer patients based on this promising approach." Sir Harpal Kumar, Cancer Research UK's chief executive, said: "Gold has been used in medicine for many years and this research adds further insight into its potential. Ensuring that treatment is accurately targeted at cancer and avoids healthy cells is the goal for much of cancer research, and this is an exciting step towards that." Dr Karen Kennedy, Director of the NCRI, said: "Research continues to shed light on how cancer cells behave and how to effectively deliver a lethal payload to the tumour. This exciting research offers that potential and needs further investigation to see how it would be used in patients. The future looks exciting with research such as this improving the way the disease is treated."


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

Tagging gold nanoparticles with a small dose of radiation has helped researchers trace the precious metal as it delivers a drug right into the heart of cancer cells, according to new laboratory research* being presented at the 2016 National Cancer Research Institute (NCRI) Cancer conference. Researchers from the CRUK/MRC Oxford Institute for Radiation Oncology have been working on better ways to transport a drug directly into the control room of cancer cells, where the chromosomes are kept. This specific drug targets a molecule - telomerase - that builds up the protective caps at the end of chromosomes called telomeres. In most cells of the body, telomeres act like an in-built timer to ensure that the cell does not live past its expiry date. Telomeres shorten each time the cell divides. Once a critical length is reached, the cell can no longer divide and it dies. Cancer cells manage to get around this safety check by reactivating telomerase allowing them to continue to grow out of control. One of the biggest hurdles in treating cancer is getting effective drugs into cancer cells, particularly to where the chromosomes are stored. Gold nanoparticles have proven to be well suited to being absorbed into cells, safely delivering drugs that could otherwise be blocked. By engineering the gold nanoparticles and adding the radioactive tracer, the researchers were able to prove that their drug was reaching the desired target in skin cancer cells grown in the lab and was shutting telomerase down, halting cancer's growth. While the radioactive tracer was used to precisely follow the drug in this study, the same method can also be used to deliver a dose of radioactivity to cancer cells, helping to kill them. This second dose is especially powerful because inactivation of telomerase makes cancer cells more sensitive to radiation. Professor Kate Vallis, lead researcher based at the CRUK/MRC Oxford Institute for Radiation Oncology, said: "Gold is precious in more than one way. We have used tiny gold nanoparticles loaded with targeted drugs to kill cancer cells in the laboratory. Our long term goal is to design new treatments for cancer patients based on this promising approach." Sir Harpal Kumar, Cancer Research UK's chief executive, said: "Gold has been used in medicine for many years and this research adds further insight into its potential. Ensuring that treatment is accurately targeted at cancer and avoids healthy cells is the goal for much of cancer research, and this is an exciting step towards that." Dr. Karen Kennedy, Director of the NCRI, said: "Research continues to shed light on how cancer cells behave and how to effectively deliver a lethal payload to the tumour. This exciting research offers that potential and needs further investigation to see how it would be used in patients. The future looks exciting with research such as this improving the way the disease is treated."


News Article | November 7, 2016
Site: www.eurekalert.org

Substantial weight gain over many years increases the risk of obesity-related cancers in men by 50 per cent and in women by almost 20 per cent, according to new research* presented at the National Cancer Research Institute's (NCRI) Cancer Conference in Liverpool, today (Monday). Researchers at The University of Manchester and The Health eResearch Centre, looked at weight gain over many years and assessed the risk of developing obesity-related cancers. This is a new way of looking at the long-term impact of being obese throughout a person's life and the link to developing cancer. In the study of approximately 300,000 people in America, including around 177,500 men and 111,500 women, researchers categorised the population into five different lifetime weight trajectories**. They looked at changes in BMI between the ages of 18 and 65. Some people gained a little weight between the ages of 18 and 65 years, while others became morbidly obese. The population was then followed up for an average of 15 years to see who went on to develop obesity-related cancers. It found that men who went from a BMI of around 22 to 27*** had a 50 per cent increased risk of developing obesity-related cancer compared to a man who stayed within a healthy weight range. And in men who went from being overweight to morbidly obese, the risk went up by 53 per cent compared to the same group. Women who went from a BMI of 23 to around 32, had a 17 per cent increased risk in comparison to women whose weight started off in the healthy bracket and remained stable. Of the 300,000 people in the study, there were around 9,400 women and 5,500 men who were diagnosed with obesity-related cancers after the age of 65. Being overweight or obese is the second biggest preventable cause of cancer in the UK after smoking and contributes to around 18,100**** cases of cancer every year. It is linked to a range of cancer types including bowel, breast, and pancreatic. Several of the obesity-related cancer types can only affect women - for example, womb cancer and ovarian cancer. Dr Hannah Lennon, lead author and researcher at The University of Manchester, said: "This research shows how important it is to look at weight gain over a person's lifetime - to give a clearer picture of cancer risk through life compared to assessing someone's BMI at a single point. "This study could also be really useful in public health. It could help identify people who would benefit the most from taking action to control their weight before any health problems arise - including a cancer diagnosis." Sir Harpal Kumar, Cancer Research UK's chief executive said: "This is a really interesting way to look at lifetime risk of obesity-related cancers and helps us understand the effects of weight gain over time. "It's important that people are informed about ways to reduce their risk of cancer. And while there are no guarantees against the disease, keeping a healthy weight can help you stack the odds in your favour and has lots of other benefits too. Making small changes in eating, drinking and taking exercise that you can stick with in the long term is a good way to get to a healthy weight - and stay there." Dr Karen Kennedy, Director of the NCRI, said: "This study provides a deeper understanding of the health implications caused by the obesity epidemic. It helps paint the picture of how risk could accumulate over time for different people, and could provide health professionals with a means to asses an individual's risk." This work is funded by Cancer Research UK as part of the National Awareness and Early Diagnosis Initiative (NAEDI). Supported by the Farr Institute and linked with the new NIHR Manchester BRC Cancer Prevention and Early Detection theme. For media enquiries contact Stephanie McClellan in the NCRI press office on 0203 469 5314 or, out of hours, on 07050 264 059. * NCRI abstract: Lifetime BMI trajectories and obesity-related cancer risk in a US retrospective cohort study http://abstracts. *** A BMI of between 18.5 and 25 kg/m^2 is considered a healthy weight; between 25-30 is overweight; over 30 is obese. For men, this is equivalent to an extra 2.5 stone increase for the average height man of 177cm between the ages of 18 and 65, because even the 'normal/reference' trajectories allows for a little weight gain as we age. This is the lean marked category compared to lean moderate category. For women example, this is the lean marked category compared to lean stable category. **** Calculated by the Statistical Information Team at Cancer Research UK, the estimated population attributable fractions overweight and obesity for cancer cases (ICD10 C00-C97, excl. C44) in the UK in 2011 using Parkin, D. M. & Boyd, L. Overweight and obesity-attributable cancer burden in the UK in 2010. Br J Cancer 2011;105 (S2):S6-S13.


SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced data from the positive, pivotal Phase III GALLIUM study that compared Gazyva® (obinutuzumab) plus chemotherapy followed by Gazyva alone head-to-head against Rituxan® (rituximab) plus chemotherapy followed by Rituxan alone for people with previously untreated follicular lymphoma. At a pre-planned interim analysis in May 2016, an independent data monitoring committee determined that the study met its primary endpoint early. The results showed Gazyva-based treatment reduced the risk of disease worsening or death (progression-free survival; PFS, as assessed by investigator) by 34 percent compared to Rituxan-based treatment (HR=0.66; 95% CI 0.51-0.85, p=0.0012). Median PFS was not yet reached. Adverse events with either Gazyva or Rituxan were consistent with those seen in previous studies. “Follicular lymphoma, the most common slow-growing form of non-Hodgkin’s lymphoma, is an incurable blood cancer characterized by cycles of remission and disease progression, and becomes harder to treat with every relapse,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “This study of Gazyva-based treatment is the first and only Phase III trial to date to show superior progression-free survival compared to Rituxan-based treatment, the current standard of care, in previously untreated follicular lymphoma.” The primary results from the GALLIUM study (Abstract #6) will be presented during the Plenary Scientific Session of the 58th American Society of Hematology (ASH) Annual Meeting in San Diego by Dr. Robert Marcus, King’s College Hospital, London and the National Cancer Research Institute (NCRI), on Sunday, December 4 at 2:00 P.M. PST. Additionally, an analysis of minimal residual disease (MRD) status in the GALLIUM study (Abstract #613) will be presented in a separate oral session by Dr. Christiane Pott, University Hospital Schleswig-Holstein, Kiel, Germany, and the German Low Grade Lymphoma Study Group (GLSG) on Monday, December 5 at 7:00 A.M. PST. GALLIUM is the third positive Phase III study for Gazyva, following the CLL11 study in patients with previously untreated chronic lymphocytic leukemia (CLL) and the GADOLIN study in patients with indolent (slow-growing) non-Hodgkin’s lymphoma whose disease progressed during or within six months of prior Rituxan-based therapy. The results of the GALLIUM study will be submitted to health authorities around the world for approval consideration. GALLIUM (NCT01332968) is a global Phase III open-label, multicenter, randomized two-arm study examining the efficacy and safety of Gazyva plus chemotherapy followed by Gazyva alone for up to two years, as compared head-to-head against Rituxan plus chemotherapy followed by Rituxan alone for up to two years. Chemotherapies used were CHOP, CVP or bendamustine and were selected by each participating study site prior to beginning enrollment. GALLIUM included 1401 patients with previously untreated indolent non-Hodgkin’s lymphoma (iNHL), of which 1202 patients had follicular lymphoma. The primary endpoint of the study was investigator-assessed PFS in patients with follicular lymphoma, with secondary endpoints including PFS assessed by independent review committee (IRC), PFS in the overall study population (iNHL), response rate (overall response, ORR; and complete response, CR), overall survival (OS) and safety. The GALLIUM study is being conducted in cooperation with the GLSG (Germany), the East German Study Group Hematology and Oncology (OSHO; Germany) and the NCRI (United Kingdom). A summary of the GALLIUM study results presented at ASH is included below. 1 Primary endpoint is PFS as assessed by investigator; median follow-up of 34.5 months 2 Measured by computerized tomography (CT) scans 3 MRD-negativity means no cancer can be detected in the blood or bone marrow using a specific highly sensitive test 4 Defined as any AE occurring during or within 24 hours of infusion of Gazyva or Rituxan and considered drug-related Follicular lymphoma is the most common indolent (slow-growing) form of non-Hodgkin’s lymphoma (NHL), accounting for about one in five cases of NHL. It is considered incurable and relapse is common. In the United States, it is estimated that more than 14,000 new cases of follicular lymphoma will be diagnosed in 2016. Gazyva is an engineered monoclonal antibody designed to attach to CD20, a protein found on certain types of B-cells. It is thought to work by attacking targeted cells both directly and together with the body's immune system. Gazyva was discovered by Roche Glycart AG, a wholly owned, independent research unit of Roche. In the United States, Gazyva is part of a collaboration between Genentech and Biogen. Combination studies investigating Gazyva with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are planned or underway across a range of blood cancers. Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that can become serious or life threatening, including: Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If a patient has had history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen for hepatitis B before, and monitor the patient for hepatitis during and after, treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes. Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. A patient’s weakened immune system could put the patient at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems. Additional possible serious side effects of Gazyva: Patients must tell their doctor right away about any side effects they experience. Gazyva can cause side effects that may become severe or life threatening, including: The most common side effects of Gazyva in CLL are infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea. The safety of Gazyva was evaluated based on 392 patients with indolent NHL (iNHL) of whom 81 percent had follicular lymphoma. In patients with follicular lymphoma, the most common side effects that were seen were consistent with the overall population who had iNHL. The most common side effects of Gazyva are infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinusitis, low red blood cell counts, general weakness, and urinary tract infection. Before receiving Gazyva, patients should talk to their doctor about: Immunizations: Before receiving Gazyva therapy, the patient should tell the patient’s healthcare provider if the patient has recently received or is scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines. Pregnancy: A patient should tell the doctor if the patient is pregnant, plans to become pregnant, or is breastfeeding. Gazyva may harm the unborn baby. Mothers who have been exposed to Gazyva during pregnancy should discuss the safety and timing of live virus vaccinations for their infants with their child’s healthcare providers. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to the doctor about using Gazyva if the patient is breastfeeding. Patients must tell their doctor about any side effects. These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist. Gazyva is available by prescription only. Report side effects to the FDA at (800) FDA-1088, or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555. Please visit http://www.Gazyva.com for the Gazyva full Prescribing Information, including Boxed WARNINGS, for additional Important Safety Information. Rituxan® (rituximab) is indicated for the treatment of patients with: People with serious infections should not receive Rituxan. It is not known if Rituxan is safe or effective in children. Patients must tell their doctor right away about any side effects they experience. Rituxan can cause serious side effects that can lead to death, including: What are the additional possible serious side effects of Rituxan? Patients must tell their doctor right away about any side effects they experience. Rituxan can cause serious side effects that can lead to death, including: The most common side effects of Rituxan are infusion reactions, chills, infections, body aches, tiredness and low white blood cells. Patients must tell their doctor if they are pregnant, plan to become pregnant or are breastfeeding. It is not known if Rituxan may harm the patient’s unborn baby or pass into the patient’s breast milk. Women should use birth control while using Rituxan and for 12 months after treatment. Patients must tell their doctor about any side effect that bothers them or that does not go away. These are not all of the possible side effects of Rituxan. For more information, patients should ask their doctor or pharmacist. Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Report side effects to Genentech at (888) 835-2555. Please visit http://www.Rituxan.com for the Rituxan full Prescribing Information, including Boxed WARNINGS and Medication Guide, for additional Important Safety Information. For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines, Genentech’s pipeline of investigational hematology medicines includes an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). Genentech’s dedication to developing novel medicines for blood diseases expands beyond oncology, with the development of the investigational hemophilia A treatment emicizumab (ACE910). For more information visit http://www.gene.com/hematology. Founded 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.


News Article | November 9, 2016
Site: www.eurekalert.org

BLOCKING a molecule could bypass bowel cancer's defence against the drug cetuximab, according to new research* presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool. Cetuximab is used to treat advanced bowel cancer, and just under half of bowel cancer patients are given the drug. While it helps many patients, there are some for whom it doesn't work at all and for others it loses effectiveness. To understand why this happens, scientists at Queen's University Belfast treated bowel cancer cells in the lab with cetuximab. They found that some cells survived the treatment by increasing the activity of a protein called ADAM17. But if they gave a drug that blocked the protein ADAM17 at the same time as cetuximab the cancer cells died. For other cancer cells, cetuximab treatment alone stopped them growing initially, but over time they became resistant and started growing again. In these cases, the cancer cells were finding a different way to outmanoeuvre the treatment that didn't involve ADAM17. Cetuximab works by blocking a molecule known as epidermal growth factor receptor (EGFR), which tells cells to grow. There are around 41,000 cases of bowel cancer diagnosed in the UK each year. And each year around 16,000 die of the disease. Dr Sandra Van Schaeybroeck, the lead researcher based at Queen's University Belfast, said: "While some bowel cancer patients respond well to cetuximab treatment, many will relapse, or not benefit from the drug. Our work shows that combining this treatment with an ADAM17 inhibitor could be a promising avenue of therapy for patients who don't respond to cetuximab by itself. "More work is needed before we can safely test this combination in patients, but the prospect of cutting off cancer's path to resistance is very exciting." Professor Peter Johnson, Cancer Research UK's chief clinician, said: "This work shows how some bowel cancer cells are able to avoid damage from a particular drug, and offers a way to prevent it. The next step is to find out whether this could work in patients." Professor Richard Wilson, Chair of the NCRI's Colorectal Cancer Clinical Studies Group, said: "Bowel cancer is the fourth most common cancer in the UK, and it's the second biggest cancer killer - so it's vital that we find ways to break through the disease's resistance to treatment." "A big issue facing bowel cancer patients is the prospect of their cancer coming back. Understanding the mechanisms that bowel cancer cells use to evade treatment with cetuximab will help us find ways to delay or prevent it recurring. This will help more people with bowel cancer live longer and with better quality of life." This research was funded by Cancer Research UK.


News Article | November 7, 2016
Site: www.sciencedaily.com

Patients with malignant melanoma -- whose disease has spread -- are more likely to respond to immunotherapy treatment if they had greater diversity in their gut bacteria, according to new research presented at the National Cancer Research Institute's (NCRI) Cancer Conference in Liverpool. Scientists at the University of Texas MD Anderson Cancer Centre studied over 200 mouth and over 100 gut microbiome samples from people who had advanced melanoma. They discovered that people whose cancer responded to immunotherapy treatment had more diversity in the types of bacteria found in their gut. They also found significant differences in the type of bacteria found in the gut of people whose cancer responded versus those who didn't. There was no difference in the type of mouth bacteria between patients. Early studies in mice have shown that changing the type of bacteria that live in the gut can improve the response to immunotherapy, but this is one of the first studies to look at the link in patients. Immunotherapy, which harness the body's immune system to target cancer cells, are an exciting avenue of cancer treatment. However, not all patients respond to these treatments, and researchers are trying to understand why. This research suggests that adapting people's gut bacteria, such as giving antibiotics, probiotics, or a faecal transplant before immunotherapy, could increase the benefits already achieved with new immunotherapy drugs now being used to treat several different types of cancer. However, this needs to be tested clinical trials. Melanoma is the fifth most common cancer in the UK with about 14,600 people being diagnosed each year. And each year about 2,300 die from the disease. Dr Jennifer Wargo, lead researcher at the University of Texas, said: "Our research shows a really interesting link that may mean the immune system is aided by gut bacteria when responding to these drugs. Not all patients respond to immunotherapy drugs and it's hard to know who will benefit from the treatment prior to it being given. "The gut microbiome can be changed through a number of different strategies, so there is real potential here to modify the gut microbiome to boost an immunotherapy response." Dr Pippa Corrie, Chair of the NCRI's Skin Cancer Clinical Studies Group, said: "There is growing evidence that gut bacteria play a vital role in warding off disease, absorbing nutrients from the food we eat, and maintaining normal function of our immune systems. "Gut microbes have been shown to influence the role of conventional chemotherapy, so it's probably not surprising that they impact on response to new immunotherapies being used in the clinic. Manipulating the gut flora may be a new strategy to enhance activity of immunotherapy drugs, as well as to manage problematic toxicity in the future."


News Article | November 10, 2016
Site: www.sciencedaily.com

Researchers have discovered that a marker found on aggressive prostate cancer cells could also be used as a way to guide treatments to the cancer, according to new research presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool. The molecule, called NAALADL2, is already measured to see if prostate cancer is likely to return, but the new study has shown that it can also help direct treatment to the cancer. The team, based at UCL, had already found that prostate cancer cells have more of the NAALADL2 molecule on their surface compared to cells from healthy tissue. Prostate cancer patients whose tumour cells have high levels of this molecule are more than twice as likely to see their disease return following surgery. In the new study, the researchers attached the drug saporin to an antibody targeted against NAALADL2 to destroy prostate cancer cells in the lab. Dr Hayley Luxton, lead researcher from the Molecular Diagnostics and Therapeutics Laboratory at University College London, said: "Using antibodies mounted with a toxic payload, we can exploit the fact that aggressive prostate cancer cells have more NAALADL2. "The next step is to further develop this for use in patients, which we hope can be done in a relatively short timeframe." Around 46,500 men are diagnosed with prostate cancer in the UK each year. And around 11,000 men will die from the disease each year. The study was funded by The Urology Foundation, John Black Charitable Trust and Cancer Research UK. Louise de Winter, CEO of The Urology Foundation, said: "This research was attractive to us as something that could potentially distinguish those so-called 'pussy cat' cancers from the 'tigers'. We're very excited by the potential shown and look forward to further findings." Dr Chris Parker, Chair of the NCRI's Prostate Cancer Clinical Studies Group, said: "When it comes to aggressiveness, prostate cancer can either be slow-growing or much faster to grow and spread. And there is an urgent need to find better treatments for the more aggressive version of the disease. "Interestingly, this study shows that the very marker that indicates a prostate tumour may be more aggressive, could also be the key to its downfall." See more at: http://abstracts.ncri.org.uk/abstract/can-we-use-n-acetyl-l-aspartyl-l-glutamate-peptidase-like-2-to-target-drugs-to-cancer-cells-2/


News Article | November 9, 2016
Site: www.biosciencetechnology.com

Researchers have discovered that a marker found on aggressive prostate cancer cells could also be used as a way to guide treatments to the cancer, according to new research presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool. The molecule, called NAALADL2, is already measured to see if prostate cancer is likely to return, but the new study has shown that it can also help direct treatment to the cancer. The team, based at UCL, had already found that prostate cancer cells have more of the NAALADL2 molecule on their surface compared to cells from healthy tissue. Prostate cancer patients whose tumour cells have high levels of this molecule are more than twice as likely to see their disease return following surgery. In the new study, the researchers attached the drug saporin to an antibody targeted against NAALADL2 to destroy prostate cancer cells in the lab. Dr. Hayley Luxton, lead researcher from the Molecular Diagnostics and Therapeutics Laboratory at University College London, said: "Using antibodies mounted with a toxic payload, we can exploit the fact that aggressive prostate cancer cells have more NAALADL2. "The next step is to further develop this for use in patients, which we hope can be done in a relatively short timeframe." Around 46,500 men are diagnosed with prostate cancer in the UK each year. And around 11,000 men will die from the disease each year. The study was funded by The Urology Foundation, John Black Charitable Trust and Cancer Research UK. Louise de Winter, CEO of The Urology Foundation, said: "This research was attractive to us as something that could potentially distinguish those so-called 'pussy cat' cancers from the 'tigers'. We're very excited by the potential shown and look forward to further findings." Dr. Chris Parker, Chair of the NCRI's Prostate Cancer Clinical Studies Group, said: "When it comes to aggressiveness, prostate cancer can either be slow-growing or much faster to grow and spread. And there is an urgent need to find better treatments for the more aggressive version of the disease. "Interestingly, this study shows that the very marker that indicates a prostate tumour may be more aggressive, could also be the key to its downfall."

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