Lecture 7 - Monoclonal Antibodies

Question 1

What is an antibody?

Answer 1

Immunoglobulin secreted by B cells (plasma cells)

Question 2

What are the 2 main parts of an antibody?

Answer 2

Fab. (Fragemtn antibody region)
Fc (fragment crystallisable region)

Question 3

What is the function of the variable fragment antigen region of the antibody?

Answer 3

Where antigens bind to the antibody

Question 4

What is the paratope?

What is the epitope?

Answer 4

Epitope = antibody binding site on antigen

Paratope = antigen binding site on antibody

Question 5

What is the fraction crystallised region of the antibody?

Answer 5

Part that binds to immmune cells

Question 6

What are the uses of monoclonal antibodies/

Answer 6

Diagnostic tests (fluorescent tags)

Therapeutics (medicines)

Question 7

What is a monoclonal antibody?

Answer 7

Mono alert antibodies which bind to the same epitope (on antigen) and are produced from a single B lymphocyte clone

Question 8

How are monoclonal antibodies produced?

Answer 8

Hybridoma technique

Question 9

What is the hybridoma technique of producing monoclonal antibodies?

Answer 9

Antigen injected into mouse, B lymphocytes producing antibodies to antigen are harvested
B lymphocytes then fused with immortal myeloma producing the hybridoma

Question 10

What are the 3 types of monoclonal antibodies/

Answer 10

Naked monoclonal antibodies
Conjugated monoclonal antibodies
Bisepcific antibodies

Question 11

What are the different types of naked monoclonal antibodies?

Answer 11

Murine (0% human)
Chimeric (65% human)
Humanised (>90% human)
Fully human

Question 12

What is the suffix for murine naked monoclonal antibodies?

Answer 12

-omab

Question 13

What is the suffix for chimeric naked monoclonal antibodies?

Answer 13

-ximab

Question 14

What is the suffix for humanised naked monoclonal antibodies?

Answer 14

-zumab

Question 15

What is the suffix for fully human naked monoclonal antibodies?

Answer 15

-umab

Question 16

What are conjugated monoclonal antibodies?

Answer 16

Where antibodies are linked to a toxic compound so the toxin can be directly delivered to the target site

Question 17

What are bispecific antibodies?

Answer 17

Where antibodies bind to 2 or more different epitopes at once

Question 18

What is an example of use of bispecific antibodies?

Answer 18

Binding to tumour antigen and T cells to bring T cell closer to tumour cell so can engage it better

Question 19

How do monoclonal antibodies generally work?

Answer 19

Bind to cell surface receptors either activating or inhibiting signalling
Bind to induce death

Surface receptor binding causing:
-antibody dependant cell mediated cytotoxicity
-complement (complement cascade) dependant cytotoxicity

Conjugate antibodies being internalised into cell (delivering toxin)

Activating T cells to destroy cancer cells

Question 20

What generally happens in antibody-dependant cell mediated cytotoxicity?

Answer 20

Antibody binds to antigen leading to phagocytosis

Question 21

What is lymphoma?

Answer 21

Blood cancer of mature lymphocytes (B cell or T cell type neoplasms)

Question 22

What type of lymphocytes does lymphoma most commonly affects?

Answer 22

B cell

Question 23

What parts of the body can be affected in lymphoma?

Answer 23

Enlarged lymph nodes
Spleen
Bone marrow
Liver
Skin
Testes
Bowel

Question 24

What are the common symptoms of lymphoma called?

Answer 24

B symptoms

Question 25

What are the B symptoms seen in lymphoma?

Answer 25

Drenching night sweats Fever > 38 Weight loss

Question 26

How do you diagnose lymphoma?

Answer 26

PET scan CT Biopsy (excision biopsy)

Question 27

What is a lymphoma called when the B lymphocytes retain the follicular pattern?

Answer 27

Follicular lymphoma (most common low grade lymphoma)

Question 28

What is the most common aggressive lymphoma which takes of the lymph node in a diffuse pattern?

Answer 28

Diffuse large B cell lymphoma

Question 29

What receptors do B cells in lymphoma express?

Answer 29

CD20

Question 30

Look at slide 19 What is the diagnosis

Question 31

Slide 20 Diagnosis?

Question 32

What are the treatment strategies in lymphoma?

Answer 32

Chemotherapy Radiotherapy Monoclonal antibody therapy Emerging new targeted therapy Stem cell transplant

Question 33

How does Rituximab used to treat lymphoma?

Answer 33

Monoclonal antibody which targets CD20 on B cells

Question 34

What type of antibody is rituximab?

Answer 34

Chimeric naked antibody

Question 35

What is a standard treatment strategy for lymphoma?

Answer 35

Chemotherapy + Steroids + Rituximab

Question 36

What is the mechanism of action of Rituximab? (what type of cytotoxicity does it stimulate?)

Answer 36

Binds to CD20 causing antibody dependant cell mediated cytotoxicity

Question 37

What are the side effects of monoclonal antibodies like rituximab?

Answer 37

Usually very well tolerated Mild fatigue Mild reaction to first infusion (due to being chimeric antibody) Very few have severe infusion related reaction

Question 38

What drugs are given if patient starts having infusion related reaction?

Answer 38

Intense facial flushing, nausea and vomiting Infusion stopped IV steroid , if still not resolved give another IV steroid Then IV metoclopramide for the nausea

Question 39

What drug is given to patients that develop an infusion related reaction towards the end?

Answer 39

Anti histamine

Question 40

How can we manage infusion related reactions?

Answer 40

Education (may still get side effects even with premedication, should inform staff if think gonna have reaction) Premedicate ( steroid, antihistamine, paracetamol) Slow infusion rate

Question 41

What is tumour lysis syndrome?

Answer 41

Where rapid tumour break down leads to lots of uric acid being released leading to Hyperuricaemia Hyperuricaemia can lead to formation of Urate crystals in the renal tubules leading to acute kidney injury which can lead to further metabolite disturbances

Question 42

What are the 3 types of monoclonal antibodies for solid cancers?

Answer 42

Trastuzumab Ipilimumab Nivolumab

Question 43

What is the mechanism of action trastuzumab in treating solid cancer?

Answer 43

Inhibitions of HER-2 signalling Good in Herceptin receptor 2 positive breast cancer

Question 44

What is the mechanism of action of nivolumab in treating solid cancer?

Answer 44

Inhibition of PD1 signalling

Question 45

What are some monoclonal antibodies used to treat autoimmune conditions?

Answer 45

Infliximab Adalimumab

Question 46

How does infliximab and adalimumab work to treat autoimmune conditions?

Answer 46

Inhibts TNF-a

Question 47

What is the main monoclonal antibody used in cardiology conditions?

Answer 47

Abciximab

Question 48

What is the mechanism of action of abciximab?

Answer 48

Inhibits the platelet glycoprotein IIb/IIIa

Question 49

What is the monoclonal antibody used to treat respiratory conditions?

Answer 49

Mepolizumab

Question 50

What is the mechanism of action of mepolizumab?

Answer 50

Inhibts IL-5

Question 51

What is. The mechanism of action ustekinumab?

Answer 51

Inhibits IL-12 and IL-23