KV 8.3 1 Passive Immunisierung und Antikörpertherapien Konteptvorlesung 3 Themenblock 8 Beda M. Stadler Institut für Immunologie Diese Folien stehen auch als PPT Files zum download bereit unter: http://www.iib.unibe.ch/wiki/?p=teaching/medical_students&l=de
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KV 8.31 Passive Immunisierung und Antikörpertherapien Konteptvorlesung 3 Themenblock 8 Beda M. Stadler Institut für Immunologie Diese Folien stehen auch.
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KV 8.3 1
Passive Immunisierung und Antikörpertherapien
Konteptvorlesung 3
Themenblock 8
Beda M. Stadler
Institut für Immunologie
Diese Folien stehen auch als PPT Files zum download bereit unter:http://www.iib.unibe.ch/wiki/?p=teaching/medical_students&l=de
Binds HER-2 (human epidermal growth factor receptor 2), a growth factor receptor found on some tumor cells (some breast cancers, lymphomas).
Over-expression of HER2 causes increased cell growth and reproduction.
HER2 protein over-expression affects approximately 25% to 30% of breast cancer patients
z.B. Herceptin® (Trastuzumab)
normal cell tumor cell treatment
KV 8.3 29
HLA-DR
TDT
CD19
CD10
CD20
CD22
CD21
CD38
Stem cell
Pro-B cell
Pre-B cells
ImmatureB cell
MatureB cell
ActivatedB cell
Plasmacell
Neoplasias: Leukemias from B-cell Precursors (B-ALL)
B-cell Lymphomas (NHL, CLL)
Multiple Myeloma
Antigen independent Antigen dependent
Strategie 1: maligne B-Zellen
KV 8.3 30
Strategie 1anti idiotypische Antikörper
(B-Z
ell L
ymp
ho
me)
KV 8.3 31
Strategie 2: Verschiedene Isotope
Nackter Antikörper Radiomarkierter Antikörper
KV 8.3 32
Isotopen markierte Antikörper
LymphoCide (anti CD22, found on some B-cell leukemias.
Tositumomab (Anti-CD20)
Lym-1 (Oncolym). Anti- HLA-DR expressed at high levels on lymphoma cells.
KV 8.3 33
A conjugate of a monoclonal antibody that binds CD33 (cell-surface molecule expressed by the cancerous cells in acute myelogenous leukemia (AML) but not found on the normal stem cells needed to repopulate the bone marrow) and calicheamicin, an oligosaccharide that blocks the binding of transcription factors (proteins) to DNA and thus inhibits transcription.
Strategie 3: Mylotarg® (anti CD-33)
KV 8.3 34
Strategie 4: Enzym markierte Antikörper
Antibody directed enzyme prodrug therapy
(ADEPT)
Tumorantigen
Tumorzelle
ZytotoxischerWirkstoff
Prodrug132
4
Enzym
Antikörper
KV 8.3 35
Strategie 5: Anti-Angiogenes
KV 8.3 36
• Recombinant humanized monoclonal antibody against VEGF; prevents binding with its receptor.
• Blocks stimulation of angiogenesis stops tumor growth.
Holgate S. et al., J Allergy Clin Immunol 2005 vol. 115 (3) pp. 459-65
anti-IgE
OmalizumabReduces IgE and FcεRI Levels
KV 8.3 44
Anti-IgE: Omalizumab (Xolair®)
KV 8.3 45
Anti Adhäsionstherapie
• Efalizumab (Raptiva®)• Anti-CD11a (subunit of LFA-1) inhibits
activation of T cells
• Alefacept (Amevive®)• binds to CD2 on memory effector T
lymphocytes, inhibiting their activation
• Abciximab (Reopro®)• Anti-Gp IIb/IIIa
KV 8.3 46
Efalizumab (Raptiva)
Interactions between leukocyte-function associated antigen type 1 (LFA-1) and intercellular adhesion molecules are important in the pathogenesis of psoriasis. Efalizumab, a humanized monoclonal antibody, binds to the subunit (CD11a) of LFA-1 and inhibits the activation of T cells