ASH News Daily - Sunday, December 11, 2011 - (Page A-15)

Saturday, December 10, 2011 Sunday, December 11, 2011 QUALITY IRON The Importance of Quality Indicators — What You Need to Know Now Center. In particular, presenters will discuss how quality indicator measures are derived, how they can be measured, the potential consequences of failure to adhere to these indicators, and the challenges that quality indicators pose to particular hematologic populations. Dr. Richard Lottenberg, Univer- By Julie PanePinto, Md, MSPh and aManda BRandow, do, MS By aManda Brandow, do, MS U A molecular mechanisms involved in mediating hepcidin’s response, has increased our knowledge of human diseases that involve an imbalance of iron and will help to direct targeted therapy. Yesterday’s Educa- This afternoon, attendees will have the opportunity to learn about the importance of quality indicators at the ASH special symposium, “Quality Indicators: Examples of Relevance to Hematology” that will be held from 2:00 to 3:30 p.m. in Room 30 of the San Diego Convention nderstanding iron homeostasis and the regulation of hepcidin, including the re established quality indicators of sufficient quality for individual populations? sity of Florida, Gainesville, will discuss the challenges in defining the quality of health care for patients with sickle cell disease (SCD). Spe- tion Program session, “Updates on Disorders of Iron Utilization and Distribution,” that is also being offered this morning at 7:30 a.m. in the Douglas Pavilion AB (Manchester Grand Hyatt), highlighted several important areas of iron homeostasis. Dr. Karin Finberg of Duke Uni- versity Medical Center discussed the molecular pathways that mediate hepcidin responses to stimuli, Hanging in the Balance: Understanding Iron Regulation And the Key to the Cause and the Cure such as iron loading, inflammation, and erythropoiesis. She noted that, in addition to these known regulators of hepcidin, both positive and negative regulation of signaling by involvement of the hepatic bone morphogenetic protein (BMP) pathway is now known to be a key mechanism in regulating hepcidin expression by the liver. On an exciting note, Dr. Finberg said that “by revealing the molecules that play cifically, Dr. Lottenberg will discuss how the small number of randomized, controlled trials in SCD poses challenges for the development of quality indicators. In addition, he will present recent developments relevant to the establishment of quality indicators in SCD and the benefits of having well-defined quality indicators in SCD. Dr. Lottenberg will highlight how operationalizing quality indicators in SCD is a work in progress, since there are real chal- key roles in hepcidin expression, these studies hold the potential to direct the development of new diagnostic tests and the design of targeted therapies for patients with iron disorders.” Following Dr. Finberg’s talk, lenges to providing SCD care even when there is strong evidence for improved outcomes. Dr. Lottenberg will also discuss An innovative approach to improving outcomes in patients with cancer This could allow potent Antibody-drug conjugates (ADCs) use a conditionally stable linker to combine the targeting specificity of monoclonal antibodies with the tumor-killing power of potent cytotoxic agents.1,2 drugs to be delivered directly to tumor cells with minimal systemic toxicity. Optimizing the parameters for clinical success Scientists at Seattle Genetics are focused on parameters critical to the effective performance of ADCs, including target antigen selection,3,4 linker stability5-7 and potent cytotoxic agents.4,7,8 and potent cytotoxic agents.4,7,8 Elements of an antibody-drug conjugate Linker Antibody specific for a tumor-associated antigen that has restricted expression on normal cells4,8 Antibody specific for a tumor-associated antigen that has restricted expression on normal cells4,8 Cytotoxic agent kills target cells when internalized and released4,8 Cytotoxic agent kills target cells when internalized and released4,8 attaches the cytotoxic agent to the antibody. Newer linker systems are designed to be systemically stable and release the cytotoxic agent in targeted cancer cells4,8,9 attaches the cytotoxic agent to the antibody. Newer linker systems are designed to be systemically stable and release the cytotoxic agent in targeted cancer cells4,8,9 Linker ADCs link precision and potency for greater activity A preclinical (in vivo) study demonstrated that the ADC is more active than the antibody alone (mAb) or the admixture (mAb + cytotoxic agent unlinked)10 A preclinical (in vivo) study demonstrated that the ADC is more active than the antibody alone (mAb) or the admixture (mAb + cytotoxic agent unlinked)10 Scientists at Seattle Genetics are focused on parameters critical to the effective performance of ADCs, including target antigen selection,3,4 linker stability5-7 Antibody-drug conjugates (ADCs) use a conditionally stable linker to combine the targeting specificity of monoclonal antibodies with the tumor-killing power of potent cytotoxic agents.1,2 drugs to be delivered directly to tumor cells with minimal systemic toxicity. This could allow potent Dr. Tomas Ganz of University of California Los Angeles focused on hepcidin and ferroportin in iron homeostasis. Hepcidin production is regulated by a complex of transferrin and transferrin receptors 1 and 2 with specialized iron-related transducer molecules HFE, hemojuvelin, and matriptase-2. These regulators interact with BMP6, the BMP receptor, and its transcriptional regulatory machinery to control hepcidin transcription. Genetic lesions in these molecules dysregulate hepcidin and are associated with the iron disorders in mouse models and in humans. The protein ferroportin functions as a transmembrane conduit for transfer of cellular iron to plasma and is expressed on professional iron exporters such as macrophages. Hepcidin binds to ferroportin on the membrane of the iron exporters inducing endocytosis and proteolysis of ferroprotin and subsequently decreased delivery of iron to the plasma. Disruption of Tweets from #ASH11 Chewing on great career development advice at #ASH11 Simultaneously exciting and ulcer-inducing... – prknlot At Successes in Bone Marrow Failures Symposium. Good session at #ASH11 – marrow Excited to hear updates from my colleagues attending @ ASH_hematology annual meeting. #ASH11 – hayeslat Loving 68 degree weather and palm trees in San diego. #ASH11 – alantanmd Meet the Editors of Hematology Web Focus Science editor en route to #ASH11. If the crew needs to ask “is there a doctor on the plane?” they will be all SET. – BioWorld The future of drug treatment in cancer Seattle Genetics is dedicated to improving the lives of people with cancer by developing innovative therapies for hematologic malignancies and solid tumors. Go to seattlegenetics.com for your complimentary, comprehensive, 15-slide educational presentation. Just click on the download icon to get the slides delivered to your personal computer or mobile device. Go to seattlegenetics.com for your complimentary, comprehensive, 15-slide educational presentation. Just click on the download icon to get the slides delivered to your personal computer or mobile device. Seattle Genetics is dedicated to improving the lives of people with cancer by developing innovative therapies for hematologic malignancies and solid tumors. Download ADC scientific slide deck > Download ADC scientific slide deck > on clinically relevant topics in benign and malignant hematology with an emphasis on articles to enhance clinicians’ understanding of a disease and the latest treatment options, is a free online service to ASH members and subscribers of Blood with a free trial available to non-members. H Leadership in antibody-drug conjugate development www.seattlegenetics.comwww.seattlegenetics.com REFERENCES: 1. Ducry L, Stump B. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem. 2010;21(1):5-13. 2. Wu AM, Senter PD. Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol. 2005;23(9):1137-1146. 3. Carter P, Smith L, Ryan M. Identification and validation of cell surface antigens for antibody targeting in oncology. Endocr Relat Cancer. 2004;11(4):659-687. 4. Carter PJ, Senter PD. Antibody-drug conjugates for cancer therapy. Cancer J. 2008;14(3):154-169. 5. Alley SC, Benjamin DR, Jeffrey SC, et al. Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjug Chem. 2008;19(3):759-765. 6. Chari RVJ. Targeted cancer therapy: conferring specificity to cytotoxic drugs. Acc Chem Res. 2008;41(1):98-107. 7. Alley SC, Okeley NM, Senter PD. Antibody-drug conjugates: targeted drug delivery for cancer. Curr Opin Chem Biol. 2010;14(4):529-537. 8. Senter PD. Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol. 2009;13(3):235-244. 9. Polson AG, Calemine-Fenaux J, Chan P, et al. Antibody-drug conjugates for the treatment of non–Hodgkin’s lymphoma: target and linker-drug selection. Cancer Res. 2009;69(6): 2358-2364. 10. Doronina SO, Toki BE, Torgov MY, et al. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol. 2003;21(7):778-784. © 2011 Seattle Genetics, Inc., Bothell, WA 98021 All rights reserved. Seattle Genetics andSeattle Genetics and Printed in USA © 2011 Seattle Genetics, Inc., Bothell, WA 98021 All rights reserved. are US registered trademarks of Seattle Genetics, Inc. US/ADC/2011/0030 US/ADC/2011/0030 are US registered trademarks of Seattle Genetics, Inc. Printed in USA REFERENCES: 1. Ducry L, Stump B. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem. 2010;21(1):5-13. 2. Wu AM, Senter PD. Arming antibodies: prospects and challenges for immunoconjugates. Nat Biotechnol. 2005;23(9):1137-1146. 3. Carter P, Smith L, Ryan M. Identification and validation of cell surface antigens for antibody targeting in oncology. Endocr Relat Cancer. 2004;11(4):659-687. 4. Carter PJ, Senter PD. Antibody-drug conjugates for cancer therapy. Cancer J. 2008;14(3):154-169. 5. Alley SC, Benjamin DR, Jeffrey SC, et al. Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjug Chem. 2008;19(3):759-765. 6. Chari RVJ. Targeted cancer therapy: conferring specificity to cytotoxic drugs. Acc Chem Res. 2008;41(1):98-107. 7. Alley SC, Okeley NM, Senter PD. Antibody-drug conjugates: targeted drug delivery for cancer. Curr Opin Chem Biol. 2010;14(4):529-537. 8. Senter PD. Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol. 2009;13(3):235-244. 9. Polson AG, Calemine-Fenaux J, Chan P, et al. Antibody-drug conjugates for the treatment of non–Hodgkin’s lymphoma: target and linker-drug selection. Cancer Res. 2009;69(6): 2358-2364. 10. Doronina SO, Toki BE, Torgov MY, et al. Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol. 2003;21(7):778-784. Just landed for #ASH11 and there is a guy in just boxers at the baggage claim... – derekwimmer Here in #ASH11 waiting T-cell lymphoma session. San Diego CA – humbertosinco Just got back from #ASH11 registration. Loved the monitor for the Twitter Feed. Are you following @ASH_hematology? Lisa_Palacios Headed out to San Diego for #ASH11. – jghoggatt 11:30 a.m. – 1:00 p.m. ASH Booth (#1315) Join the annual meeting conversation on Twitter. Use #ASH11 in your tweets from the meeting. Follow ASH on Twitter (@ash_hematology) for Society news, meeting information, advocacy updates, and much more. Dr. Joel Ann Chasis University of California Lawrence Berkeley National Laboratory Dr. Sagar Lonial Emory University For more information, go to www.hematologywebfocus.org. 10/25/11 2:37 PM10/25/11 2:37 PM – Kind of geeking out that #ASH11 has its own iPhone app! – deepfriedlard ematology Web Focus, a quarterly, Web-based publication that focuses »» IRON Page A-18 the need to be aware of unintended consequences when developing quality indicators for SCD. “There needs to be validation of outcome measures. We need to assure quality indicators serve to enhance the capabilities of providers, rather »» QUALITY Page A-18 ASH NEWS DAILYAIL Page A–15 ® ® http://www.hematologywebfocus.org/ http://www.hematologywebfocus.org

Table of Contents for the Digital Edition of ASH News Daily - Sunday, December 11, 2011

ASH News Daily - Sunday, December 11, 2011

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