Checkpoint proteins Flashcards
What inhibits t-cell activation? Where does this occur? What is the consequence for the t-cell and in cancer?
T-cell upregulated CTLA-4 which binds to the CD80/86 on the APC cell.
In the lymph node
Cell cycle arrest
Tumours will be resistant to therapy and to any immune response
What makes T-cells proliferate, differentiate and eventually lead to the effector function?
CD28 on t-cells and CD80/86 on APC bind, polarizing signal from CD4 cells and MHC with peptide on APC
What are the types of t-cells?
CD4, CD8, and regulatory t-cells
After T-cell is activated what happens?
It matures and APC or t-cell migrates out of the lymph node to the tumour site and kills it
What are possible therapeutic possbilities to stop t-cell inhibition?
Anti-CTLA4,
Was anti-CTLA-4 effective in therapy?
In melanoma cancer
How is anti-CTLA4 made?
It’s a monoclonal antibody that’s from mouse but fully humanized
How is the antibody administered?
As a vaccine with a peptide or just with ab or just peptide
Which is more effective ab+peptide or just ab?
Using peptide with AB or just AB is more effective than just peptide. But not much of difference if peptide and AB combination compared to AB treatment alone
What is a more effective therapy rather than just peptide vaccine?
IL-2 with the peptide or peptide with AB was more effective
What can they conclude on using peptide along with AB for treatment about teh immune system?
The immune system is functional and active already just needs anitibody to block inhibition
What are the problems with using anti-CTLA4
Toxicities because the antibody is non specific
Which organs has the highest toxicity incidence because of anti-CTLA4?
Skin, GI tract, liver, pituitary
What is another checkpoint inhibitor? What does it inhibit?
PDL1-PDL2 found on tumour cells binds to PD-1 on tumour cells. Another one is TIM3
What is advantage PD1 AB have on CTLA4 AB? And why is this difference seen?
It’s less toxic.
Becuase the PD1 get upregulated in mature T-cell which is transported out of teh lymph node, therefore these antibodies only target these differentiated t-cell at tumour site.
