Engineering Antibodies 2

Question 1

When was rituximab first used?

Answer 1

1992

Question 2

What was rituximab originally used for?

Answer 2

Follicular lymphoma - now used for all forms of B cell non-Hodgkins lymphoma

Question 3

What type of antibody is rituximab?

Answer 3

Anti-CD20 - chimeric antibody

Question 4

What is CD20?

Answer 4

A transmembrane glycoprotein found on developing B cells

Question 5

What are rituximabs mechanisms of action regarding apoptosis?

Answer 5

Apoptosis
- turns on a intracellular signals (Cross linking CD20), leads to MAP kinase activation and calcium influx disturbing mitochondria

Question 6

What are rituximabs mechanism of action for complement mediated cellular cytotoxicity?

Answer 6

Complement binds to antibody once it has bound to surface

Question 7

What are side effects of rituximab?

Answer 7

Allergy
Infections risk - HSV, CMV etc.
Leukopenia
Dermatological/mucosal surface reactions
Gut and cardiovascular issues
Renal and respiratory issues

Question 8

What are indications to discontinue rituximab?

Answer 8

JC virus is in the brain but suppressed in most people
Reactivation of hepatitis B and development of progressive multi focal leukoencephalopathy due to JC virus means discontinue rituximab

Question 9

What are some other uses of rituximab?

Answer 9

Autoimmunity - rheumatoid arthritis

Question 10

How does rituximab help with rheumatoid arthritis?

Answer 10

Helps remove auto reactive B cells

Question 11

What are problems with rituximab used in rheumatoid arthritis?

Answer 11

Few problems - some risk of increased infections, poor response to vaccine, late-onset neutropenia, moderate drop in antibody levels

Question 12

What happens if you take frucose groups off rituximab?

Answer 12

Does better ADCC

Question 13

What is the fully human bio similar of rituximab?

Answer 13

Ofatumumab

Question 14

What wasn’t worth carrying on with rituximab bio similars?

Answer 14

Anti-CD20 fragment bound to a different molecule to stabilise it, couldn’t compete with other biosimilars

Question 15

What can omalizumab be used for?

Answer 15

Anti-IgE in asthma and allergy

Question 16

What does omalizumab bind to and not bind to?

Answer 16

Binds to low affinity IgE receptor and free IgE
Doesn’t trigger mast cells

Question 17

What is an example of a natural bio specific antibody?

Answer 17

IgE due to arm exchange

Question 18

What are good engineered bio specific antibody examples?

Answer 18

Catumaxomab, blinatumomab and emicizumab

Question 19

What are examples of use of bsAbs?

Answer 19

Cell-cell
Dual receptor interactions
Co-factor mimics
Piggybacking to target usually inaccessible sites

Question 20

What does emicizumab bind?

Answer 20

Factor IXa and X

Question 21

What does emicizumab do?

Answer 21

Replaces factor 8 in the clotting cascade , treatment for factor 8 deficient haemophilia A patients, reduces bleed events

Question 22

What does blinatumumab do?

Answer 22

Treats B cell acute lymphoblastic leukemia
Supports T cell driven killing of tumour cells

Question 23

What does blinatumumab target?

Answer 23

Has two light chains - one targets CD3, the other targets CD19

Question 24

What are the two types of linker technology?

Answer 24

Cleavage - a peptide linker cleavable
Non-cleavable - releases after degradation of the antibody structure

Question 25

What do antimitotics do?

Answer 25

Play with microtubules

Question 26

Wbat does calicheamicin do?

Answer 26

Causes strand breakage in DNA

Question 27

What does trastuzumab-emtansine do?

Answer 27

Targets HER2 receptor, causes mitosis arrest and cell death. Is a Microtubule inhibitor

Question 28

What does gemtuzumab ozogamicin target?

Answer 28

Anti-CD33 for acute myeloid leukaemia

Question 29

What does gemtuzumab ozogamicin do?

Answer 29

Conjugated to calcheamicin, it is released and reduced by glutathione into its active form and DNA stand breakages leads to repair mechanisms