Clinical Uses Of Cytokines (and Anti-cytokines) Flashcards
(34 cards)
What is the problem with the functional roles of cytokines?
They are pleomorphic, have multiple effects on multiple different cell types
What are direct effects of cytokines?
Change proliferation rate of target cell e.g. interferons anti-proliferative for leukaemia cells
What regulatory effects can cytokines have?
Change cell activity e.g. IL15 stimulation of NK and cytotoxic T cells
Change the nature of a response e.g. CD4+ switching
What are the 3 different forms of receptor for IL-2?
Low affinity just alpha chain
IL-2 receptor beta chain that interacts with common gamma chain
High affinity receptor - alpha, beta, gamma all expressed on same surface at the same time
Why may it be difficult to achieve desired response to cytokines by systemic administration of high doses?
Because cytokines generally work in an autocrine or paracrine way
How can cytokines be produced in other biologics?
Bacterial expression
Eukaryotic expression
What is the considerations for bacterial expression cytokines?
Folding correct
No glycosylation - doesn’t always matter
What is the consideration for cytokines with eukaryotic expression?
Glycosylation, but may not be perfect
How can you produce a cytokine using recombinant DNA methods and what are the pros?
Use of cloned gene (ensures biologically active protein is produced)
Not glycosylated
Opportunity for modification
Large scale production is possible
What is the con of making cytokines by recombinant DNA methods?
Expensive
What is the substitution to make a cytokine more stable?
Substitution of serine for cysteine in IL2
What was the first cytokine to be produced by recombinant technology?
IL2
What were the applications for IL-2?
Stimulating T and NK responses in renal cell carcinoma, melanoma
What does IL2 act on?
T regs , ILC2
What do low concentrations of IL2 tend to do?
Be more of a drive towards Treg
What do high concentrations of IL2 tend to do?
Push production of effector cells
What can blocking IL2 or CD25 common gamma chain do?
Trigger drive towards autoimmune response
What do the mutated versions of IL-2 now interact with?
Instead of high affinity receptor, they interact more with moderate affinity receptor
What happens when you stimulate the medium affinity receptor for IL-2 more?
Tends to stimulate cytotoxic T cells and NK cells rather than Tregs whihc is better in cancer treatment
How do you increase half life of IL-2?
Adding on albumin
How many antibdoies can bind IL-2 with their antigen combining sites?
Two
What do antibodies binding to IL-2 do?
Biases activation either towards strong immune response or more tolerance, so dont have to use mutated versions of IL-2
What does polyethylglyclo do to cytokines?
Gives better half-life
What does cytokines linked to Fc portion do?
Increases stability and also may be able to target particular cell types
