Wk.9 L3 - Antibodies

Question 1

LO

Answer 1

• Describe the structure of a typical antibody molecule.
• Describe the different formats of therapeutic antibodies.
• Describe the mechanisms of action of different types of therapeutic antibodies.
• Describe challenges associated with developing therapeutic antibodies.
• Describe ways we can build better or different therapeutic antibodies

Question 2

Antibodies or Immunoglobulins

Answer 2

Proteins produced by B-cells in response to antigens

Antibodies bind to specific antigens, allowing immune system to neutralise antigens, marking them for destruction

Question 3

Antibody structure

Answer 3

Y-shaped

Composed of four polypeptide chains:
- two heavy (H) + two light (L) chains

Fab(Variable region): Fragment antigen binding
- Antigen epitope recognition & binding

Fc(Constant region): Fragment crystallisable
- Interaction with immune effector cells

[heft]

Question 4

Antibody function

Answer 4

• Neutralisation
• Antibody-dependent cellular cytotoxicity (ADCC)
• Antibody-dependent cellular phagocytosis (ADCP)
• Complement-dependent cytotoxicity (CDC)

[heft]

Question 5

Polyclonal

Answer 5

• Mixture of different antibodies recognising different epitopes of the same antigen
• Derives from multiple clones of B-cells

Question 6

Monoclonal

Answer 6

Identical antibodies that typically bind to an epitope/ antigen from a single clone of immune cells

Question 7

Recombinant

Answer 7

Genetically engineered

Question 8

Therapeutic Antibodies: Format

Answer 8

Antibody (monospecific)
Antibody (Bispecific)
Drug-conjugated
Toxin-conjugated
Radioisotope-conjugated

Question 9

monospecific antibodies mechanisms of action

Answer 9

Target cell binders OR immune checkpoint blockers
- Disruption of survival signal of cells
- Activation of immune cells
- Inhibit pathways, negatively regulating T-cells

Question 10

bispecific antibodies mechanisms of action

Answer 10

• Can recognise 2 different antigens on different cells, bringing them close together to activate the T-cell
• Can recognise 2 different antigens on same cell, blocking antigens & maximise the anti-tumour activity
• T-cell engager OR non…

Question 11

The 3 Different Conjugates mechanisms of action

Answer 11

Linking a tumour targetting antibody to a cytotoxic drug

Question 12

Challenges & Future Directions

Answer 12

• Immune responses: Anaphalaxis etc.
• Therapeutic antibodies recognised as “foreign” causing reactions
• Costs, scalability, stability, delivery, drug resistance

Question 14

Building better or different therapeutic antibodies

Answer 14

Do engineering of the FC region
- Where antibodies interact with effector cells
- Can increase the half life
- Enhance ADCC
- Modulate affinity

Conjugates
Multi-specific antigens
- Target multiple regions on T-cells for a stronger response
- Target multiple antigens on tumour for higher affinity and selectivity