Lecture 24 - Biological therapy for respiratory disease Flashcards
What is a biological therapy?
Any pharmaceutical therapy except that of small molecules (less than 100 daltons)
How are exosomes produced?
invagination of plasma membrane, captures moelcules.
develpoed as a means of communication between cells
Why are exosomes exciting?
modified exosomes can be used for packaging, used to transport sRNA into tissues - also used to cross the epithelial barrier and hence could be used via inhalation
Biosynthetic exosomes can deliver nucleotides to the lung, which are usually hard because of their size and charge
What are some novel protein scaffold technologies?
Anti-calin - complexed to digitoxigenin
Adnection - complexed to IL-23
Avimer scaffold - has multimeric potential which gives high affinity
VHH nanbodyes (from camels) has also been exploited
BiSpecific T cell engager - (bite)-like structures, brings the T cell towards the tumour cell
The small protein scaffolds, have shorter half lives, but have properties that would allow them to be used where Ig have difficulty…
penetrating - important when considering inhalation
What is pulmonary alveolar proteinosis (PAP)?
rare autoimmune disease casuing deficiency of GM-CSF activity
causes reduced macrophage/neutrophil clearance of surfactant protein leads to fluid accumulation and impaired gas exchange
How can PAP be treated?
lung lavage - invasive and difficult
but now may be treated with recombinant GM-CSF (an inhaled version is being trialled)
What is the objective when using mesenchymal stem cells?
repair and anti-inflammation action (sources of IL-10, TGFB1)
Where are Vaccines relevant for lung disease?
targeting combating exacerbation of asthma and COPD
reduce amount of infection with influenza for instance
unfortunately no vaccine for Rhinovirus yet…
Why are pseudo-typed lentivirus useful in CF treatment?
They can insert in cells that AREN’T dividing (i.e in a quiescent state)
further engineering with an M2 coat protein will allow it to cross mucosal layers (to help with uptake)
Hypersecretion of mucos can cause…
Which interleukin is responsible for this?
airway obstruction (this is a result in IL-13 signalling)
IL-13 can also stimulate Periostin - which is why it is a biomarker of IL-13
Where is there interest in cytokine targeting in asthma?
When it is not fully controlled by long acting beta-agonists and inhaled cortico-steriods = severe asthma
What are some cytokine targeting agents?
Lebrikizumab is directed against IL-13
prevents it from interacting with the IL-4 receptor, therefore diminishes IL-13 signalling
Used on top of standard of care (LABA/ICS/CysLT1blocker)
IL4-Receptor-alpha is a common receptor to which interleukins?
IL-4 and IL-13
blocking prevents action of both
What are the advangates of biologics?
Selectivity, potentiall lesser burden of adverse effects
shorter development time
long half life
