BC - L4

Question 1

Topics discussed?

Answer 1

about mAbs
how mAbs are made
mechanisms of action
limitations of mAbs

Question 2

What are monoclonal antibodies? Why do they have great therapeutic potential?

Answer 2

a pure population of antibodies with one target specificity made by a clonal population of antibody secreting plasma cells

extremely well tolerated
long lived
very specific & selective

Question 3

Describe how the first mAbs were made

Answer 3

-

Question 4

Humanisation of mAbs?

Answer 4

to avoid HAMA
fully mouse (-o-)
replace mouse IgH & IgL C-region with human (-xi-)
graft mouse VH & VL CDR onto human framework (-zu-)
graft one V CDR, other V chimeric (-xizu-)
only human, XenoMouse (-u-)

Question 5

Describe new generation mAb pathway

Answer 5

-

Question 6

Describe humanisation via isolation

Answer 6

-

Question 7

Describe humanisation using bacteriophage display

Answer 7

-

Question 8

Mechanisms of action?

Answer 8

ligand blockade
receptor blockade
depletion
target cell activation

Question 9

ligand blockade examples? how they work? (3)

Answer 9

anti-TNFa (infliximab, adalimumab)
anti-VEGFA (bevacizumab)
anti-RANKL

Question 10

receptor blockade examples? how they work? (1)

Answer 10

anti-HER2 (Trastuzumab)

Question 11

depletion examples?

Answer 11

anti-CD20 (Rituximab)

Question 12

how does target cell activation work?

Answer 12

T cell activating

Question 13

limitations?

Answer 13

unpredictable effects
cardiotoxicity
infections
acute anaphylaxis
generation of anti-mAb antibodies