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Immune Monitoring

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Autoimmune diseases affect 50 million in the US, and are one of ... Chimeric CD20 Mabs. Founders of Trubion Pharmaceuticals. Program for. Autoimmune. Disease ... – PowerPoint PPT presentation

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Title: Immune Monitoring


1
Program for Autoimmune Disease Intervention
(PADI)
Innovative Programs to Advance Health Research
(LSDF 07-02)
  • Immune Monitoring Targeted Therapeutics

Interdisciplinary translational research applied
to autoimmune diseases to improve health outcomes
2
Program for Autoimmune Disease Intervention
  • Unmet medical need
  • Scientific opportunities
  • Economic growth opportunities

3
Autoimmune Diseases
Myasthenia gravis Pernicious anemia Polyarteritis
Polychondritis Polymyositis Psoriasis Rheumatoid
arthritis Scleroderma Sjogrens syndroms Stiff
man syndrome Giant cell Arteritis Ulcerative
colitis Vasculitis Uveitis Vitiligo
Autoimmune Diabetes Multiple sclerosis Lupus Alope
cia areata Ankylosing spondylitis Addisons
disease Hemolytic anemia Autoimmune
Hepatitis Thrombocytopenic purpura Behcets
disease Pemphigus Crohns disease Dermatomyositis G
raves disease Hashimotos Thyroiditis
4
Program for Autoimmune Disease Intervention
  • Unmet medical need

Autoimmune diseases affect 50 million in the US,
and are one of the top 10 leading causes of death
in children and women age 65 and younger.
5
Program for Autoimmune Disease Intervention
  • Unmet medical need

Morbidity and mortality are directly related to
late diagnosis, lack of effective treatments, and
problems in access to care
6
Program for Autoimmune Disease Intervention
  • Scientific Opportunity

Morbidity and mortality are directly related to
late diagnosis, lack of effective treatments, and
problems in access to care
7
Program for Autoimmune Disease Intervention
  • Scientific Opportunity
  • We now, for the first time, can identify,
    isolate, and study the cells (specific
    lymphocytes) which trigger and cause autoimmune
    diseases

8
Enabling Technology co-opt molecular
mechanisms responsible for immune specificity
9
Precise molecular handshakes provide the
cell-to-cell contacts responsible for immune
specificity
10
Precise molecular handshakes provide the
cell-to-cell contacts responsible for immune
specificity
11
Mimic the bodys molecular strategy
12

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Early treatment is the goal Early identification
of autoimmunity is the key
Immune activation
Progressive loss of islet cells
Genetic Predisposition
Surviving islet cells
Normal insulin release
Overt diabetes
Glucose normal
Time ?
15

16
The therapeutic window for intervention using
immunomodulation
Immune activation
Progressive loss of islet cells
Genetic Predisposition
Surviving islet cells
Normal insulin release
Overt diabetes
Glucose normal
Time ?
17
The therapeutic window for intervention using
immunomodulation
18
The Pipeline of Immunotherapy Trials in New Onset
Type 1 Diabetes
  • Rapamycin and IL-2
  • Phase III Anti-CD3
  • Anti-CD3 and Exanitide
  • GAD 65 in Alum
  • Proinsulin DNA Vaccine
  • ATG
  • Anti-CD3 and insulin
  • MMF and DZB
  • HSP 65 p277
  • Multi-dose DZB
  • Exanitide and DZB
  • Multidose anti-CD3
  • Anti-CD20
  • CTLA4-Ig

19
Program for Autoimmune Disease Intervention
  • type 1 diabetes and multiple sclerosis and lupus?
  • Related by
  • genetic susceptibility,
  • molecular mechanisms,
  • potential therapeutics directed at fundamental
    immune pathways

20
TGEM Tetramer Guided Epitope Mapping
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Patient blood sample for analysis
60
FACS staining with pooled tetramer of
VP16-stimulated PBMC
Tetramers loaded with single peptide
FACS staining with peptide-specific tetramer
Overlapping peptides
Pooled peptides
Pooled tetramers
21
Program for Autoimmune Disease Intervention
  • Our vision for this Program is to evaluate new
    and emerging markers of lymphocyte lineage and
    function, in combination with new and emerging
    markers of genetic propensity for autoimmune
    phenotypes, in patients at all stages of
    autoimmune diseasefrom predisposition through
    disease diagnosis and response to immunotherapy.

22
Health Impact DeliverablesA toolkit for a new
approach to autoimmunity
23
Program for Autoimmune Disease Intervention
  • We anticipate that a successful result from this
    Program will be the widespread use of such
    profiling tools for early diagnosis, selection of
    therapy, monitoring of therapy, and design of the
    next generation clinical trials for T1D, MS, and
    lupus.

better outcomes reduced costs
24
Program for Autoimmune Disease Intervention
  • Scientific Opportunity

Morbidity and mortality are directly related to
late diagnosis, lack of effective treatments, and
problems in access to care
25
Mimic the bodys molecular strategy
26
Program for Autoimmune Disease Intervention
  • Autoantigen targeting the PADI
    interdisciplinary approach to novel autoimmune
    therapy

27
Program for Autoimmune Disease Intervention
  • Immediate benefits

Morbidity and mortality are directly related to
late diagnosis, lack of effective treatments, and
problems in access to care
28
Program for Autoimmune Disease Intervention
State-wide network of collaborating
providers Access to trials, Education of patients
and families
29
Program for Autoimmune Disease Intervention
  • Key LSDF elements
  • Institutional Commitment
  • Partnerships with other organizations
  • Financial cost-sharing
  • Deliverables
  • Milestones
  • Commercialization plan

30
Program for Autoimmune Disease Intervention
  • Economic track record

Jeffrey Ledbetter Martha Hayden-Ledbetter Edward
Clark
  • Inventors of abatacept (CTLA4Ig)
  • Chimeric CD20 Mabs
  • Founders of Trubion Pharmaceuticals

31
Program for Autoimmune Disease Intervention
  • Jane Buckner Translational Medicine
  • Carla Greenbaum Clinical Trials
  • Heather Shilling Genotyping Core
  • Keith Elkon (UW) Lupus targeting
  • Mark Wener (UW) Lupus clinic
  • Mariko Kita Multiple Sclerosis
  • Jerry Nepom Immunomonitoring

32
www.benaroyaresearch.org
  • Translational Immunology
  • Registry-repository-autoimmunity-allergy-asthma-ma
    trix biology
  • Clinical Trials
  • NIDDK TrialNet, NIAID ITN, JDRF, SWOG, IIT (VM)
  • 215 employees
  • 20 senior scientists
  • 26 million/year research volume
  • 65 from competitive research grants
  • the rest from pharma/biotech, donations,
    endowment
  • Formerly the Virginia Mason Research Center, est
    1956
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