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Immunity > Lecture 7 - Monoclonal Antibodies > Flashcards

Lecture 7 - Monoclonal Antibodies Flashcards

1
Q

What is an antibody?

A

Immunoglobulin secreted by B cells (plasma cells)

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2
Q

What are the 2 main parts of an antibody?

A

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

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3
Q

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

A

Where antigens bind to the antibody

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4
Q

What is the paratope?

What is the epitope?

A

Epitope = antibody binding site on antigen

Paratope = antigen binding site on antibody

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5
Q

What is the fraction crystallised region of the antibody?

A

Part that binds to immmune cells

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6
Q

What are the uses of monoclonal antibodies/

A

Diagnostic tests (fluorescent tags)

Therapeutics (medicines)

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7
Q

What is a monoclonal antibody?

A

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

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8
Q

How are monoclonal antibodies produced?

A

Hybridoma technique

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9
Q

What is the hybridoma technique of producing monoclonal antibodies?

A

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

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10
Q

What are the 3 types of monoclonal antibodies/

A

Naked monoclonal antibodies
Conjugated monoclonal antibodies
Bisepcific antibodies

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11
Q

What are the different types of naked monoclonal antibodies?

A

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

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12
Q

What is the suffix for murine naked monoclonal antibodies?

A

-omab

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13
Q

What is the suffix for chimeric naked monoclonal antibodies?

A

-ximab

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14
Q

What is the suffix for humanised naked monoclonal antibodies?

A

-zumab

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15
Q

What is the suffix for fully human naked monoclonal antibodies?

A

-umab

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16
Q

What are conjugated monoclonal antibodies?

A

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

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17
Q

What are bispecific antibodies?

A

Where antibodies bind to 2 or more different epitopes at once

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18
Q

What is an example of use of bispecific antibodies?

A

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

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19
Q

How do monoclonal antibodies generally work?

A

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

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20
Q

What generally happens in antibody-dependant cell mediated cytotoxicity?

A

Antibody binds to antigen leading to phagocytosis

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21
Q

What is lymphoma?

A

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

22
Q

What type of lymphocytes does lymphoma most commonly affects?

A

B cell

23
Q

What parts of the body can be affected in lymphoma?

A

Enlarged lymph nodes
Spleen
Bone marrow
Liver
Skin
Testes
Bowel

24
Q

What are the common symptoms of lymphoma called?

A

B symptoms

25
Q

What are the B symptoms seen in lymphoma?

A

Drenching night sweats
Fever > 38
Weight loss

26
Q

How do you diagnose lymphoma?

A

PET scan
CT
Biopsy (excision biopsy)

27
Q

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

A

Follicular lymphoma (most common low grade lymphoma)

28
Q

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

A

Diffuse large B cell lymphoma

29
Q

What receptors do B cells in lymphoma express?

A

CD20

30
Q

Look at slide 19

What is the diagnosis

A
31
Q

Slide 20

Diagnosis?

A
32
Q

What are the treatment strategies in lymphoma?

A

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

33
Q

How does Rituximab used to treat lymphoma?

A

Monoclonal antibody which targets CD20 on B cells

34
Q

What type of antibody is rituximab?

A

Chimeric naked antibody

35
Q

What is a standard treatment strategy for lymphoma?

A

Chemotherapy
+
Steroids
+
Rituximab

36
Q

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

A

Binds to CD20 causing antibody dependant cell mediated cytotoxicity

37
Q

What are the side effects of monoclonal antibodies like rituximab?

A

Usually very well tolerated

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

38
Q

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

A

Intense facial flushing, nausea and vomiting

Infusion stopped

IV steroid , if still not resolved give another IV steroid
Then IV metoclopramide for the nausea

39
Q

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

A

Anti histamine

40
Q

How can we manage infusion related reactions?

A

Education (may still get side effects even with premedication, should inform staff if think gonna have reaction)

Premedicate ( steroid, antihistamine, paracetamol)

Slow infusion rate

41
Q

What is tumour lysis syndrome?

A

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

42
Q

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

A

Trastuzumab
Ipilimumab
Nivolumab

43
Q

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

A

Inhibitions of HER-2 signalling

Good in Herceptin receptor 2 positive breast cancer

44
Q

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

A

Inhibition of PD1 signalling

45
Q

What are some monoclonal antibodies used to treat autoimmune conditions?

A

Infliximab
Adalimumab

46
Q

How does infliximab and adalimumab work to treat autoimmune conditions?

A

Inhibts TNF-a

47
Q

What is the main monoclonal antibody used in cardiology conditions?

A

Abciximab

48
Q

What is the mechanism of action of abciximab?

A

Inhibits the platelet glycoprotein IIb/IIIa

49
Q

What is the monoclonal antibody used to treat respiratory conditions?

A

Mepolizumab

50
Q

What is the mechanism of action of mepolizumab?

A

Inhibts IL-5

51
Q

What is. The mechanism of action ustekinumab?

A

Inhibits IL-12 and IL-23

Immunity (9 decks)

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