Therapeutic Proteins - Fitz

Question 1

What are fusion proteins?

Answer 1

2 or more genes joined with recombinant DNA technology

Question 2

What is the point of PEGylation?

Answer 2

significantly increase half life!!

Question 3

What are peptibodies?

Answer 3

Use structure of antibodies as scaffold to build proteins that interact with a receptor, with-out activating immune system

Question 4

Chimeric antibodies

Answer 4

Variable region is mouse, constant region is human

30-35% mouse

Question 5

Humanised antibodies

Answer 5

only complementary-determining regions mouse, rest human

10% mouse

Question 6

Do cytokines have a short or long half life?

Answer 6

SHORT! very short!

Question 7

What are some advantages to antibody therapy?

Answer 7

Specificity - increased theraptutic index

Every epitope is potentail target

longer term benefit to short term therapy

diagonstic reagents

Question 8

How are Abs administered?

Answer 8

Given IV, extremely LONG HALF LIFE!!

Question 9

What are common side effects to Ab therapy?

Answer 9

Infusion reactions
Type III hypersensitivity reactions
Cytokine release syndrome
Infections (reactivation of TB)

Question 10

What is HAMA?

Answer 10

Human anti-mouse antibody

Seen in Type III hypersensitivity reactions

Question 11

U-MAB

Answer 11

from human

Question 12

O-MAB

Answer 12

from mouse

Question 13

XI-MAB

Answer 13

chimeric

Question 14

ZU-MAB

Answer 14

humanized

Question 15

VIR

Answer 15

viral traget

Question 16

BAC

Answer 16

bacterial target

Question 17

LIM

Answer 17

immune target

Question 18

LES

Answer 18

infectious lesions target

Question 19

CIR

Answer 19

cardiovascular target

Question 20

What are the two strategies for antibody design?

Answer 20

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

Question 21

What are the big disadvantages to cytokine therapy?

Answer 21

Short serum half life (minutes)

Extremely potent biological modifiers- invoke complicated cascades that result in unpredictable and undesirable effects

Question 22

What do erythroid growth factors do?

Distinguish beween
Erythropoietin
Darboepoetim
MPEG-epoetin

Answer 22

-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

Question 23

Filgrastim MOA?

Answer 23

(G-CSF)

Stimulates production of neutrophils with-in bone marrow

Question 24

Sagramostim MOA?

Answer 24

(GM-CSF)

Stimulates myelopoiesis in general (monocytes specifically)

Question 25

What do megakaryocyte growth factors do?

Answer 25

increase platelet production

Question 26

What are the pros and cons of PEG’d compounds?

Answer 26

Pro= much longer half life!!

Con= decreased immunogenicity and antigenicity

Question 27

Interleukin 11 increases production of what?

Answer 27

platelets