Checkpoint Inhibitors Flashcards
what first-line treatment did Merck announce to significantly improve progression-free survival
Pembrolizumab
what cancer is pembrolizumab primarily a first-line treatment for
colorectal cancer
what is another name for pembrolizumab
Keytruda
name 2 hallmarks of cancer
- sustaining proliferative signalling
- evading growth suppressors
- activating invasion and metastasis
- enabling replicative immortality
- inducing angiogenesis
- resisting cell death
what is an APC?
antigen presenting cell
what do effector t-cells do?
recognise tumour antigens
what 4 mechanisms do tumours use to evade the immune system?
- inhibition of tumour antigen presentation
- dysregulation of immune cell activity
- secretion of immunosuppressive factors
- recruitment of immunosuppressive cell types
why is it risky to target cyclins?
all cells use cyclins to regulate their behaviour
what part of the tumour regards biotherapeutics
the periphery / extracellular portion
name two checkpoint antibody inhibitors
- anti-CTLA4
- anti-PD1 / anti-PDL1
what is an anti-PD1 antibody?
pembrolizumab
what is an anti-CDLA4 antibody?
ipilimumab
what were the names of the two scientists who won the nobel prize in physiology in 2018?
Allison and Honjo
what does immune checkpoint therapy target?
regulatory pathways in T cells to enhance anti-tumour immune responses
how many signals does it take to activate T cells?
two
what does the T cell receptor (TCR) and antigen create on the tumour or epithelial cell?
an immune synapse which leads to no T cell proliferation
what role do immune checkpoints, such as PD1 and CTLA4 play in regulating immune responses?
immune checkpoints act as inhibitory pathways that regulate immune responses, maintaining self-tolerance and preventing excess immune activation
how does interaction between PD1 and PDL1 inhibit T-cell activity?
when PD1 on T cells bind to PDL1 on tumour cells or antigen-presenting cells, it sends an inhibitory signal that reduces T cell activity, allowing tumours to evade immune destruction
what is the MoA of Ipilimumab in treating melanoma?
it blocks the CTLA4 receptor on T-cells, enhancing the immune response by promoting T cell activation and proliferation, improving the body’s ability to attack melanoma cells
what is the difference between primary and secondary resistance to checkpoint inhibitors?
primary resistance occurs when patients fail to respond to checkpoint inhibitors from the start, whereas secondary resistance develops after an initial response, often due to adaptive immune mechanisms or changes in tumour biology
how do combination therapies enhance the efficacy of checkpoint inhibitors in cancer treatment?
combination therapies, such as using checkpoint inhibitors with chemotherapy or targeted therapies, can modulate the tumour microenvironment or increase the immunogenicity of tumours, enhancing immune response
what are the potential side effects of checkpoint inhibitor therapy, and how are they managed?
immune-related adverse effects such as colitis, hepatitis, or pneumonitis, which are managed through immunosuppressive therapies like corticosteroids
why are neoantigens important for effectiveness of checkpoint inhibitors?
these are tumour-specific mutated proteins that are recognised by the immune system, and their presence can enhance the efficacy of checkpoint inhibitors by promoting stronger T-cell responses
what is the role of the Fc region in the therapeutic efficacy of mAbs used in checkpoint inhibition?
the Fc region can recruit immune effector functions such as ADCC or complement activation, enhancing anti-tumour response
