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
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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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