CE L4 Biologicals

Question 1

What do biologicals target in RA

Answer 1

mopping-ip TNF

Question 2

MAB =

Answer 2

monoclonal antibody

Question 3

2 e.g of biological therapies for RA

Answer 3

Infliximab

Adalimumab

Question 4

What does Enbrel (Etanercept) do?

Answer 4

soluble TNF receptor

Question 5

What is the difference between polyclonal and monoclonal?

Answer 5

Harvesting a mix of different ab types - polyclonal

Isolating a particular B cell producing ONE ab type - monoclonal

Question 6

Ab are produced against …………………….. so we need to isolate one.

Answer 6

each different epitope of the antigen

Question 7

what does anti ICAM do?

Answer 7

blocks adhesion molecules

blocks T cell migration

Question 8

problem with antiICAM?

Answer 8

initial response but later pt developed immune complexes

Question 9

Chimeric antibodies are produced replacing the consistant parts in … and ….. regions with human sequence?

Answer 9

Fc and F

Question 10

The ligand binding region on chimeric ab is murine or human?

Answer 10

Murine

Question 11

Fully humanised ab are made by……

Answer 11

immunising transgenic mice carrying human Ig genes
OR
in vitro recombination in bateriophages

Question 12

Advantage of fully humanised ab?

Answer 12

Reduced immunogenic reaction

Question 13

Soluble receptor idea involves….

Answer 13

increasing the circulating amount of soluble receptor to mop-up free cytokines

Question 14

Problems with soluble receptors (3)

Answer 14

• rapidly cleared from circulation
• homotrimic TNF can still link membrane bound receptors with soluble receptor bound
• may facilitate signal transduction
  (also: sIL-1RI exacerbates disease by binding to other receptor)

Question 15

how do you make a fusion protein? (2)

Answer 15

dimerise two soluble receptors with PEG
OR
link soluble receptor to Fc domain of Ig

Question 16

What is the point of fusion proteins? (2)

Answer 16

extends half life

can bind two molecules of TNFalpha, prevents rec interaction

Question 17

2 e.g. of fusion proteins?

Answer 17

lenercept and entanercept

Question 18

Etanercept is administerd

Answer 18

sub cut twice a week (also used for juvenile onset arthritis)

Question 19

Disadvantages of immunotherapy

Answer 19

ALL OF THE MONEY
reactivation of infection
doesn't cure the disease
suppression of bone marrow
tachyphylaxis (less with humanised)

Question 20

Cytokine therapies are used to…

Answer 20

bost host defese

Question 21

What cytokines are in cytokine therapies?

3

Answer 21

IL4
IL10
IL13

Question 22

What do cytokine therapies downregulate?

3

Answer 22

TNF
IL1
IFNgamma

Question 23

advantage of cytokine therapy over mabs?

Answer 23

generally not immunogentic

Question 24

problem with cytokine therapy

Answer 24

narrow therapeutic window

Question 25

advantages of gene therapy

Answer 25

not degraded like injected protein

- tissue specific promoters are used - potetially inhibit NFkB or FADD

Question 26

disadvantages of gene therapy

Answer 26

need to be able to switch gene on or off

rapid, transient effects

Question 27

What is Anakinra?

Answer 27

Recombinant non-glycosylated form of IL1Ra

sustained relief of RA

Question 28

problem with anakinra?

Answer 28

not effective in all patients

further tests of s/e needed

Question 29

That gene therapy has been trialed?

Answer 29

IL1-Ra gene into the joint - injection into one joint decreased information in others