Lecture 24 - Biological Therapies for Respiratory Disease Flashcards Preview

Frontiers in Biomedicine > Lecture 24 - Biological Therapies for Respiratory Disease > Flashcards

Flashcards in Lecture 24 - Biological Therapies for Respiratory Disease Deck (20):
1

Definition of a biological therapy

All pharmaceutically-based therapies that aren't small molecules (under 1kDa)

2

Nucleotide biological therapies

Anti-sense oligonucleotides such as siRNA, shRNA constructs.

3

Possible uses for nucleotide biological therapies

Therapies for CMV, familial hypercholesterolaemia (ApoB)

4

Current focus of research on nucleotide biological therapies

Focus on packaging and delivery

5

Potential siRNA delivery system

Exosome delivery

6

Recent alternative to monoclonal antibody therapies

Novel protein scaffold technologies.
Proteins that can act like MAbs, but aren't destroyed in nebulisation process of administration

7

Examples of novel protein scaffold technologies
1)
2)

1) Adnectin - Fibronectin domain bound to IL-23
2) Bivalent diabodies - Bivalent T cell engager (bite) domain binds TCR, tumour cells, leading to cytotoxic killing of tumour cells

8

Example of a disease that is treatable with recombinant proteins
1)
2)
3)

1) Pulmonary alveolar proteinosis.
2) A rare autoimmune disease leading to a deficiency in GM-CSF.
3) Leads to a reduction in neutrophil and macrophage clearance of surfactant in the lungs. Fluid accumulation, impaired gas exchange.

9

How might pulmonary alveolar proteinosis be treated?

Half of PAP patients have autoantibodies against GM-CSF. These patients can be treated with recombinant GM-CSF

10

Advantages and disadvantages of protein scaffolds vs MAbs

Protein scaffolds have a shorter half-life than MAbs, but can be nebulised without being destroyed, therefore can be inhaled.

11

Example of a cell therapy for COPD

Mesenchymal stem cells. These repair tissue, have anti-inflammatory action.
Sources of IL-6, IL-10, TGFb

12

Biomarker for epithelium IL-13 activity

Periostin

13

Role of IL-13
1)
2)
3)

1) B cell isotype switching to IgE
2) Increases number of mucus-secreting cells in airways
3) Activates fibroblasts, increases periostin secretion, which further activates fibroblasts

14

Aim of pharmaceutical treatments of severe asthma

Treatments should either spare the need for steroids, or have a complementary action

15

Monoclonal antibody can binds to IL-13

Lebrikizumab

16

Effect of lebrikizumab

Binds to IL-13, prevents it from binding to IL-13R.
Reduces symptoms of severe asthma in patients with high periostin levels

17

Signalling molecules triggered by IL-13/IL-13R binding

Jak1, Tyk2.
Stat6/stat6 homodimer

18

Way to block both IL-4 and IL-13 action

Block IL-4Ralpha subunit.
This is a subunit of both IL-4R and IL-13R

19

Advantages of cytokine targeting in asthma
1)
2)
3)
4)

1) Selective.
2) Reduces burden of adverse events
3) Shorter development time, more predictable development success.
4) Long half-life

20

Disadvantages of cytokine targeting in asthma
1)
2)
3)

1) High cost of production
2) Must be parenterally administered
3) Many targets are intracellular