Checkpoint Inhibitors Flashcards
What characteristic of trastuzumab have to allow for infrequent dosing?
Long serum half life
What is the loading dose of trastuzumab?
8mg per kg followed by 6mg per kg (IV) over a 90min period every 3rd week
Can you effectively clear solid tumours?
No there is always minimal residual disease
What are 3 reasons for trastuzumab resistance?
steric effects
alternative elevations of other receptor tyrosine kinases
intracellular alterations
What does KEYTRUDA target?
The immune system
What are the 6 OG hallmarks of cancer?
Sustaining proliferative signaling
evading growth suppressors
activating invasion & metastasis
enabling replicative immortality
inducing angiogenesis
resisting cell death
What does the APC do?
Recognise tumour cell
What are 4 ways tumours can evade the immune system?
Inhibition of APC
Dysregulation of immune cell activity
secretion of immunosuppressive factors
recruitment of immunosuppressive cell type
What are 2 emerging hallmarks?
Deregulating cellular energetics
avoiding immune destruction
What are 2 enabling characteristics of the new hallmarks?
Genome instability & mutation
Tumour promoting inflammation
What regulates cell cycle?
Cyclin
What is the survival of tumours assisted by?
Checkpoint immunomodulation to maintain imbalance between immune surveillance & cancer cell proliferation
What are 3 checkpoint antibody inhibitors?
anti-CTLA-4
anti-PD-1
anti-PD-L1
Is the antigen + MHC only being presented to a TCR sufficient for T cell proliferation?
No - need B7 & CD28 costimulation
What 2 checkpoint molecules abrogate T cell responses?
PD-1
CTLA-4
What does antibody blockade of immune checkpoints enhances?
T cell responses
What cytokine is produced to lead to PDL-1 expression on tumour cells?
IFN-gamma
Which type of antibody is showing most progress for checkpoint therapy?
Blocking antibodies
What is the MoA of inhibitory receptors?
regulate CTL activation & effector functions to sustain self-tolerance & minimize bystander tissue damage
What was the furst immune checkpoint inhibitor?
Ipilimumab as an anti CTLA-4 antibody for melanoma
What are the 2 classes of immunotherapy that is FDA approved?
PD-1 inhibitor
CTLA-4 inhibitor
Whats an example of an Anti-PD1 drug?
Nivolumab
What is an example of an anti-PD-L1?
Avelumab
