Immune Checkpoint Inhibitors Flashcards
What is immunotherapy?
a type of biological therapy
a cancer treatment that helps the immune system fight cancer
stimulate immune response
relieve immune inhibition
What is the difference between immunotherapy and other therapies?
chemotherapy: targeting fast dividing cells
targeted therapy: targeting a key molecule involved in tumor cell proliferation, growth, survival and/or invasion
What are immune checkpoints?
regulators of the immune system
preventing indiscriminative attacking of cells by the immune system
essential for self-tolerance
What are the stimulatory checkpoint molecules?
CD28
CD80 (B7-1)
CD86 (B7-2)
4-1BB (CD137)
CD27
CD40
What are the inhibitory checkpoint molecules?
CTLA-4 (CD152)
PD-1
B7-H3 (CD276)
B7-H4 (VTCN1)
BTLA (CD272)
KIR
What is the correlation between cancer cells and immune checkpoints?
cancer cells can evade immune attacks by stimulating the inhibitory immune checkpoint targets
Describe CTLA-4.
upregulated in T cells upon exposure to antigen
checkpoint molecule that inhibits immune response
binding B7-1 or B7-2
higher binding affinity than CD28
-CTLA-4: low abundance and high affinity, not expressed by resting T cells
-CD28: high abundance and low affinity, expressing constitutively in T cells
What happens when CTLA-4 is blocked?
stimulate immune system and kill cancer cells
What happens when there is binding between PD-1 and PD-L1?
inhibits immune response
-PD-L1 expression helps tumor cells escape the immune system surveillance
What is the target of ipilimumab?
CTLA-4
What is the indication for ipilimumab?
melanoma
malignant pleural mesothelioma
What is the general tolerance to ipilimumab?
better tolerance than chemotherapy
What is the target of tremelimumab?
CTLA-4
What is the indication for tremelimumab?
hepatocellular carcinoma
metastatic non-small cell lung cancer
What is the target of nivolumab?
PD-1
What is the indication for nivolumab?
melanoma
malignant pleural mesothelioma
NSCLC
advanced renal cell carcinoma
urothelial carcinoma
classical Hodgkins lymphoma
hepatocellular carcinoma
What is the target of pembrolizumab?
PD-1
What is the indication for pembrolizumab?
melanoma
NSCLC
head and neck squamous cell cancer
classical Hodgkins lymphoma
large B-cell lymphoma
urothelial carcinoma
gastric cancer
hepatocellular carcinoma
What is the target of cemiplimab?
PD-1
What is the indication for cemiplimab?
metastatic cutaneous squamous cell carcinoma
locally advanced CSCC
limited in “cold” tumors
What is the target of atezolizumab?
PD-L1
What is the indication for atezolizumab?
locally advanced or metastatic urothelial carcinoma
metastatic NSCLC
locally advanced or metastatic triple-negative breast cancer
What is the target of avelumab?
PD-L1
What is the indication for avelumab?
metastatic Merkel cell carcinoma
metastatic NSCLC
locally advanced or metastatic urothelial carcinoma
advanced renal cell carcinoma
What is the target of durvalumab?
PD-L1
What is the indication for durvalumab?
urothelial carcinoma
NSCLC
What are the atypical patterns of response?
pseudo-progression
-a response to treatment after initial increase in volume of cancer lesions, due to infiltration of tumoral tissue by immune cells
-immunotherapy does not generate a rapid response
-response to tx, when obtained, will last over time due to the immunological memory
hyper-progression
-acceleration of tumor growth during immune checkpoint inhibition
What are the adverse reactions to immune checkpoint inhibitors?
most common: rash, diarrhea, fatigue
rarer:
-change in skin color due to skin inflammation
-cough and chest pain due to lung inflammation
-belly pain and diarrhea due to colon inflammation
-diabetes due to pancreatic inflammtion
-hepatitis due to liver inflammation
-nephritis due to renal inflammtion
What is the target of relatimab?
LAG-3
-an inhibitory receptor overexpressed in exhausted T cells
What is relatimab used in combination with?
nivolumab
