Immune checkpoint modulation Flashcards
who received a Lasker award in 2015
James Allison
James Allison won a Lasker award for his discovery
discovery and development of monoclonal antibody therapy that unleashes the immune system to combat cancer
what sort of immunotherapy did J. Allison develop
T-cell checkpoint protein inhibition
During T-cell activation by APC
positive an negative signals occur
CTLA4 is an
immune checkpoint protein
CTLA4
prevents overly intense response that might damage normal cells
blocking immune checkpoint proteins e.g. CTLA4
releases the breaks on the immune system- increasing its ability to destroy cancer cells
costimualtion via CD28 on T cells when MHC presents to TCR
traduces T cell activating signals
CTLA4 ligation on activated T cells
down-regulates T cell responses by binding to B7
blocking CTLA4 ligation with an antibody
enhances T cell responses
name an anti-CTLA4 mAb
Ipilimumab
Ipilimumab
first immune modulation drug to get approval for advanced cell melanoma
ipilimumab
blocks the activity of a checkpoint protein CTLA4 which is expressed on the surface of activated cytotoxic t cells
- increasing T cell activation
mAbs can be used to inhibits
inhibitory receptors
novolumab
approved for patients with advanced melanoma or lung cancer
what does novolumab
bind to PD-1, which is an inhibitory receptor, to allow the cytotoxic killing of tumour cells
example of an immunotherapy trial which went wrong
theralizumab - TGN1412
where did the trial take place
Northwick Park
what was TGN141 being designed to be used for
rheumatoid arthritiis
TGN1412 ends to
CD28
CD28
costimualtor pair on T cells
TGN1412 was a
potent agonist- stimulating anti-infallamtory cytokine production e.g. 1l-10
what did TGN141 cause
severe inflammatory reaction due to cytokine release syndrome