1
Q
Name 5 novel therapeutic strategies of immunotherapy
A
- Biologics
- Adjuvants
- Allergy Immunisation
- Helminithic therapy
- Cancer therapy
- T-cell engineering
2
Q
Name 4 conventional immunosuppressive drugs
A
- Corticosteroids
- Cytotoxic drugs
- Cyclosporin A
- Rapmycin
3
Q
How do corticosteroids work?
A
Inhibit inflammation
- Inhibit transcription of inflammatory genes
- Promote transcription of anti-inflammatory genes
4
Q
How do Cytotoxic drugs work?
A
Interfere with DNA synthesis
- Non specific - e.g., azathioprine, cyclophosphamide, mycophenolate
5
Q
How does Cyclosporin A work?
A
suppresses IL-2 - inhibits T-cell proliferation
- via NFAT
6
Q
How does rapymycin work?
A
Inhibits mTOR pathway - inhibits cell proliferation, translation and auto-Nagy
7
Q
Definition of Immunotherapy
A
Treating disease via immune modulation - activation, suppression or skewing
8
Q
4 methods of immunotherapy
A
- Soluble mediators - cytokines, cytokine antagonists, adjuvants
- Antibody therapy - receptor/ligand blocking
- Cell based - DC vaccination/ genetic engineering of T-cells
- Skewing/suppression
9
Q
4 examples of cytokines in immunotherapy
A
- GM-CSF/G-CF (growth factors) - treats neutropenia in cancer patients - increases WBCs
- PEGylated interferon alpha - treats hepatitis B/C (viral infection)
- Bone marrow donors - injection - increases WBCs
- Interferon gammar - treats CGD patients - activates macrophages/neutrophils
10
Q
3 examples of cytokine antagonists
A
- Anakinra - soluble IL-1 receptor antagonist - targets auto inflammatory diseases
- Rilonacept - IL-1-Fc fusion protein
- Etanercept - recombinant TNF-alpha receptor-fusion protein
11
Q
3 examples of adjuvants
A
- CpG (ligand) - imiquimod - cancer/warts
- Beta glucans - yeast cell walls
- Hypomethylated DNA - activate toll-like receptors - useful for viral/type-1 response
12
Q
what is CTLA-4 and what do CTLA-4 inhibitors do?
A
- CTLA-4/CD152 protein receptor - is an immune checkpoint and downregulates immune responses
- Checkpoint inhibitors - like anticancer drugs block CTLA-4 - which inhibits T-cell costimulation
13
Q
3 examples of the therapeutics of monoclonal antibodies
A
- Anti-TNF-alpha - major pro inflammatory cytokine (infliximab)
- B-cell leukaemia anti-CD20 - (Rituximab)
- Breast cancer - anti-HER2/neu receptor - (Herceptin/trastuzamab)
14
Q
Modes of action of monoclonal antibodies
A
- Ligand/receptor blocking
- Induction of apoptosis
- Complement mediated killing
15
Q
Problems with monoclonal antibodies
A
- Expensive
- Hard to copy
- Repeat doses are often immunogenic - neutralising anti-antibody antibodies
- Can humanise antibody - but keeps loops as mice/rat - which are less immunogenic
16
Q
What is the role of adjuvants?
A
- Enhance immune response
- Upregulate costimulatory molecules - increase migration and presentation to DCs - increases longevity of antigen
- pore proteins are not immunogenic - so you need to add adjuvants
- magnitude and type of response can be manipulated via coupling and type of adjuvant used
17
Q
What is squalene used for ?
A
- Is a lipid - added to adjuvants as soluble adjuvants can be cleared by circulation easily
18
Q
How are allergies caused? (1 point)
A
- Excessive Th2 immunity
- Th2/IgE mediated response activate mast cell degranulation - and cause inflammation and tissue damage
19
Q
How can immunotherapies prevent allergies?
6 points
A
- By suppressing/skewing the Th2 response to a Th1 response
- By immunising APC or DC
- Enhancing Th1 = Switches off Th2
- Stops generation of IgE
- Can use mutated allergens - with agonists - leads to IgG response e.g., CpG/TLR4
- Higher dosage of allergen - T reg cells can switch off Th2 response
20
Q
Why is dangerous too inject allergens? (1 point)
What can you do to stop this? (1 point)
A
- Can cause anaphylactic shock
- Can inject anti-IgE therapy
21
Q
Examples of diseases caused by excessive Th1/Th17 immunity? (4 points)
A
- Inflammatory bowel disease
- Type 1 diabetes
- Multiple sclerosis
- Rheumatoid arthritis
22
Q
What are helminths and what are they used for?
2 points
A
- are parasitic worms
- Can be used to skew immune system from Th1 to Th2 - so Th2 will regulate Th1
- uses dendritic cells
23
Q
How do you use tolergenic dendritic cell therapy to suppress the immune response and what can it prevent? (3 points)
A
- Remove DCs and grow in growth factor - to form tolergenic DCs.
- Inject into human - helps switch off T cells directly, generate T reg cells (to switch off T cells) or cause T cells to undergo apoptosis
- prevent allergy or inflammatory type 1/2 disease
24
Q
What is transplantation and name 2 methods?
A
- Prevention of transplant rejection
- Can use long term immunosuppressives or short term
25
What are used as long term immunosuppressives and why are they not good?
- Corticosteroids
| - Can mean patient is immunocompromised for a long time
26
How do short term immunosuppressives work?
And name 3 examples? ( 3 points)
- Induce T cell unresponsiveness - 'reset' tolerogenic mechanisms
- Campath-1 monoclonal antibody
- Basiliximab - prevents T cell activation (anti-IL-2 receptor)
- Non-FcR binding anti CD3 monoclonals - anti-alpha-Beta- TcR monoclonals
27
How do tumours grow? (2 points)
- Create anti-inflammatory environment - switch off immune cells
- use inhibitory receptors that switch them off
28
Name 4 ways to enhance immune response against cancerous tumours? (4 points)
- Checkpoint inhibitors - inhibit the inhibitory receptors
- Monoclonal antibodies - anti-CD20 (B-cells), anti-erb2 receptor (block growth receptors), anti-VEGF - stop oxygen and nutrient availability for tumours
- Soluble mediators - GM-CSF - enhance blood cells - after bone marrow transplant
- Imiquimod - TLR 7/8 agonist - enhance anti-tumoural/antiviral response
29
Why are tumours hard to vaccinate against?
| 2 points
- They are very immunosuppressive - switch off immune system
| - Lots of normal cells have the same receptors as tumours - don't want to kill them too
30
Name 4 ways we can overcome tumour suppression? (4 points)
- Activate T cells - blockade inhibitory receptor on T-cells - allows their activation
- Block IL-10/TGF-beta - adoptive transfer of IL-2 treated cells
- Up regulate MHC1-IFNgammar treatment
- Engineer 'super T cells' - highly active (Dont require MCH1)
31
Name and describe a novel anti-tumour strategy
| 1 point
- Dendritic cell vaccination therapy
| - Remove DCs - add adjuvants - reinject
32
Explain 'super' T cell/Car-T therapy (2 points)
- Engineer antigen binding part of antibody onto T cell receptor
- Add activatory domains to T cell receptor - which adds many activation signals - as tumours can deactivate T cells
33
Why is antibody-CD3 good? (2 points)
- Is a hybrid - circumvents need for MHC1 for T cell activation
- So the tumours antigen no longer need to be protein derived
34
How can NK cells be used for treating tumours?
| 2 points
- Increases the homing and maturation of NK cells - by changing sugars on surface/homing receptors
- Create CAR receptors - for NK cells
35
Explain host-directed therapy - for infectious disease
| 3 points - virus, bacteria, fungi
- Doesn't target pathogen - targets host
Viruses - Uses interferon therapies - Targets host dependent life cycle - unlikely this will mutate - no resistance
Bacteria - e.g., tuberculosis - promotes phagosome maturation - induces antimicrobial peptides - targets inflammatory response and prevents resistance
- Fungi - statins - reduces cholesterol/ergoesterol
36
What is TGN1412? (1 point)
- It activated all T cells - caused huge inflammation
| - Example of immunotherapy going wrong
Immunolgy
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