Therapeutic Proteins - Fitz Flashcards
What are fusion proteins?
2 or more genes joined with recombinant DNA technology
What is the point of PEGylation?
significantly increase half life!!
What are peptibodies?
Use structure of antibodies as scaffold to build proteins that interact with a receptor, with-out activating immune system
Chimeric antibodies
Variable region is mouse, constant region is human
30-35% mouse
Humanised antibodies
only complementary-determining regions mouse, rest human
10% mouse
Do cytokines have a short or long half life?
SHORT! very short!
What are some advantages to antibody therapy?
Specificity - increased theraptutic index
Every epitope is potentail target
longer term benefit to short term therapy
diagonstic reagents
How are Abs administered?
Given IV, extremely LONG HALF LIFE!!
What are common side effects to Ab therapy?
Infusion reactions
Type III hypersensitivity reactions
Cytokine release syndrome
Infections (reactivation of TB)
What is HAMA?
Human anti-mouse antibody
Seen in Type III hypersensitivity reactions
U-MAB
from human
O-MAB
from mouse
XI-MAB
chimeric
ZU-MAB
humanized
VIR
viral traget
BAC
bacterial target
LIM
immune target
LES
infectious lesions target
CIR
cardiovascular target
What are the two strategies for antibody design?
Inhibit a protein to suppress normal function
Recruit the patient’s immune system to attack and destroy cells that are selectively expressing a particular protein
What are the big disadvantages to cytokine therapy?
Short serum half life (minutes)
Extremely potent biological modifiers- invoke complicated cascades that result in unpredictable and undesirable effects
What do erythroid growth factors do?
Distinguish beween
Erythropoietin
Darboepoetim
MPEG-epoetin
-regulates proliferation of red blood cell progenitors
Erythropoietin- short half life
Darbepoetin - heavily glycosylated, longer half life
MPEG-epoeitn - covalently attached PEG polymer,longest half life
Filgrastim MOA?
(G-CSF)
Stimulates production of neutrophils with-in bone marrow
Sagramostim MOA?
(GM-CSF)
Stimulates myelopoiesis in general (monocytes specifically)
What do megakaryocyte growth factors do?
increase platelet production
What are the pros and cons of PEG’d compounds?
Pro= much longer half life!!
Con= decreased immunogenicity and antigenicity
Interleukin 11 increases production of what?
platelets
