Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

BIOM30002 - M2M > Lecture 5 - mAbs > Flashcards

Lecture 5 - mAbs Flashcards

1
Q

Which cell type produces Ig and is used in the lab as an ‘Ig producing factory’?

A

Plasma cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a monoclonal antibody?

A

A population of Ab’s from a single B cell clone

i.e., they all have the same specificity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What factors give mAbs great therapeutic potential?

A
  • Well tolerated (come from us)
  • Very high specificity
  • Long-lived
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the half-life of Ab?

A

Several weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which types of diseases are mAbs mainly used for at the moment?

A
  • Malignancies

* Auto-immune conditions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are ‘The Big 5’ mAbs?

A
  • Adalimumab (Anti-TNF)
  • Infliximab (Anti-TNF)
  • Trastizumab (Anti-HER2)
  • Bevacizumab (Anti-VEGFA)
  • Rituximab (Anti-CD20)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the name of Anti-TNF?

A

Remicade (Infliximab)

Humira (Adalimumab)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the name for Anti-CD20?

A

Rituximab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the name for Anti-VEGFA?

A

Avastin / Bevacizumab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the name for Anti-HER2?

A

Herceptin / Trastuzumab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What recognition did the researchers who came up with mAbs receive?

A

Nobel Prize for Medicine in 1984

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the process of harvesting mAbs from mice

A
  1. Mice spleen cells + myeloma cells
  2. Fusion
  3. Hybridomas
  4. Culture in drug
  5. Selection of positive cells
  6. Harvest of mAbs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the shortcomings of mAbs from mice?

A
  • They are recognised as foreign and thus have a short half life
  • The ‘mice’ constant region means that they are lacking some effector functions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe ‘Humanisation’ of mice mAb

A
  1. CDR grafting in vitro
    • Mouse variable region grafted onto human constant region
    • Ig are fully human apart from the CDRs
    • Longer half life in serum (than fully mouse)
2. Transgenic mice
 • Have human Ig genes
 • Challenge mice with antigen
 • Mice produce human Ig
 • Very good half life
  1. Harvesting from humans
    • Harvest B cells from immune individual
    • Fuse with EBV to immortalise cells
    • Screening to select for the desired specificity
    • Ig isolation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How good are humanised mAbs raised in vitro?

A

Still fairly crude

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe mAbs raised in transgenic mice

A

Transgenic mice:
• have human Ig genes (C or V & C)

These mAbs are really good because they contain barely any mice parts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe mAb generation from humans

A
  1. Infected human with high affinity, IgG
  2. Memory cells collected
  3. Immortalisation: Memory cells infected with EBV
  4. Screening
  5. mAbs harvesting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the advantages and disadvantages of mAbs from infected humans?

A

Pros:
• not rejected by patients
• mAbs have specificity that was effective at clearing the infection

Cons:
• Specificities limited to foreign immunogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are human mAbs most often used for?

A

Passive immunisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the pros of passive immunisation?

A

Useful when a very quick immune response is needed (HIV, SARS, influenza)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is ‘naked mAb’ useful for?

A

ADCC: Antibody dependent cell-mediated cytotoxicity
CDC: cell dependent cytotoxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are some ways we can ‘arm’ mAbs?

A 
Multistep targeting:
 • Bispecific mAb
Immunoconjugates:
 • Radioimmunoconjugate
 • Immunocytokine
 • Immunotoxin
 • Immunoliposome
 • Cellular immunoconjugates
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe Radioimmunoconjugates

A

Radioactive substance conjugates to a mAb which is specific for a tumour cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Describe Immunocytokines

A

Cytokine conjugated to a mAb specific for a tumour cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Describe Cellular immunoconjugates
mAb bispecific for tumour cell and killer cell | This brings the killer cell right to the tumour cell
26
What are the mechanisms of action of mAbs?
1. Ligand blockade 2. Receptor blockade 3. Target cell depletion 4. Target cell activation
27
Which mAb is used against Rheumatoid arthritis, psoriasis & Crohn's disease?
Anti-TNFa: • Remicade (Infliximab) • Humira (Adalimumab)
28
Which mAb is used for anti-angiogenesis and cancer therapy?
Anti-VEGFA: | • Avastin (Bevacizumab)
29
Which mAb is used for Breast cancer?
Anti-HER2: | • Herceptin / trastuzumab
30
Which mAb is used for Rheumatoid arthritis and non-Hodgkins lymphoma?
Anti-CD20: | • Rituximab
31
Describe the mechanism of action of anti-TNFa
* "Ligand blockade" * mAb specific for TNF (pro-inflammatory cytokine) * TNF bound by mAb, so it can't bind to TNF-R on inflammatory cells
32
Describe improvement in Rheumatoid arthritis with Remicade
Increased function of joints compared to patients not taking the drug
33
What is the role of TNF-a in Rheumatoid arthritis?
* Strong pro-inflammatory cytokine | * Leads to joint destruction
34
Describe the success of Avastin / Bevacizumab
mAb used in cancer, anti-angiogenesis agent * Better survival rates compared to conventional therapy * However, benefit is not that great * Not a cure
35
Describe the function of anti-RANKL mAbs
Denozumab * "Ligand blockade" * Specific for RANKL, which is a factor that increases the action of osteoclasts * By blocking RANK-L, we decrease bone resorption in Multiple Myeloma
36
Which cancer cells produce lots of RANK-L?
Myeloma cells
37
Where is RANK?
Osteoclasts
38
What are some examples of mAb ligand blockade?
* Anti-TNF-α (Adalimumab, Infliximab) * Anti-RANK-L (Denosumab) * Anti-VEGFA (Bevacizumab)
39
Describe receptor down-modulation
When receptors are engaged a lot, they are taken back into the cell and degraded, in order to down regulate the response
40
What are some examples of mAb receptor blockade or down-regulation?
Receptor down regulation: Anti-HER2 • HER2 is a receptor in malignant breast cancer cells • Tumour growth is suppressed by blocking the receptor
41
What is HER-2? | In which disease is it overactive?
* Epidermal GF receptor | * Breast cancer
42
What are some ways that depletion occurs?
Anti-CD20 • MAC formation • ADCC • Phagocytosis
43
Which cells express CD20?
All B cells
44
Describe the action of Rituximab
* mAb specific for CD20 | * Brings about transient depletion of ALL B cells
45
Describe the effectiveness of Rituximab
50% remission of B cell lymphoma (eg. non-Hogdkins lymphoma) patients
46
What is combination therapy?
Conventional treatment + mAb
47
What was Rituximab's initial use, and what is it used for now?
Started off as a cancer therapy | Now used for auto-immune conditions
48
What is Rituximab specific for?
CD20
49
What is Herceptin specific for?
HER2 | aka Trastuzumab
50
What is Remicade specific for?
TNFα | aka Infliximab
51
What is Avastin specific for?
VEGFA
52
Describe mAbs used for cell activation What is significant about this? Give examples
``` • mAbs specific for parts of T cells • When engaged, lead to activation of T cells (**T cell activation without antigen!**) → • more T cell cytotoxicity • more T cell help eg. ``` 1. Anti-CD3 2. Anti-CD28 → this didn't end well 3. Anti-CTLA4
53
What happened with the first in man trials of Anti-CD28?
Massive cytokine storm and organ failure in the 6 healthy subjects
54
What is Ipilimumab, and what disease is it used for?
Anti-CTLA4 | Used in metastatic melanoma
55
What is CTLA4?
Expressed on the surface of T cells after activation by DCs to prevent further activation
56
What is the effect of Anti-CTLA4?
Blockage of inhibition of T cell activation | → More T cell activation
57
What are some limitations of mAbs as therapeutics?
* Anti-CD28 disaster * Cardiotoxicity * infections (in immune cell depletions) * Anti-mAb antibodies (loss of efficacy)
58
What is an orphan disease?
Rare diseases with limited treatment development
59
Describe the structure of CARs
Chimeric antigen receptors * External Ab 'for specificity) * Intracellular T cell activation section
60
Describe how CARs could be used to treat disease
(Chimeric antigen receptor) 1. T cells isolated from patient 2. Viral vector delivers anti-CD19 CAR gene to T cells 3. T cells in culture express anti-CD19 CAR 4. Lymphocytes killed in patient 5. CAR expressing T cells reinstated in patient 6. CAR expressing T cells recognise B cells (through CD19) and induce CTL killing 7. Depletion of B cells Used for CLL & Follicular lymphoma
61
How are the CARs put into T cells?
Viral vector
62
What is the effect of CAR therapy in B cell cancers?
Complete depletion of B cells
63
On which cells is CD19 expressed?
All lymphocytes
64
What is IL-1β?
Pro-inflammatory cytokine ``` Brings about systemic features of inflammation: • fever • pain • malaise • tissue damage ```
65
Which diseases is Anti-IL1β used for? What is the mechanism of action? How has it been received in patients?
Used for CAPS: a collection of rare autoimmune disorders Mechanism of action: • Ligand blockade ``` In patients: • Complete response within 7 days • Well tolerated • Long lasting • No side effects ```
66
What are 'off-label' trials?
A drug becomes licensed for one rare disease, and then is use in trials for more common diseases. This is what happened with Rituximab and now for Anti-IL1β mAbs
67
What other disorders is Anti-IL1β being used for?
• Juvenile idiopathic arthritis • Gout • Late onset Type 2 Diabetes (chronic inflammatory conditions)
68
Describe the mechanism of B cell depletion with Anti-CD20 (Rituximab)
→ mAb binds to CD20 1. ADCC • IgG(1) binds to CD20 • NK cells bind IgG with IgγR I • NK cells induce apoptosis of B cell ``` 2. Complement activation • IgM binds to CD20 • Activation of Cq1 • Complement cascade • Formation of membrane attack complex ``` ``` 3. Phagocytosis • Ig binds to CD20 • Phagocytes binds Ab with FcR • Phagocytosis • Intracellular killing in phagosome ```
69
What is the mechanism of action of Anti-VEGFA?
Ligand blockade
70
Which class are monoclonal antibodies?
IgG1
71
What is the nomenclature for the following: • Chimaeric mAbs • CDR grafted (humanised) mAbs • Fully human mAbs?
Chimaeric mAbs: -xi- CDR grafted (humanised): -zu- Fully human: -u-

BIOM30002 - M2M (36 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions