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PHAR211 > Immune Checkpoint Inhibitors > Flashcards

Immune Checkpoint Inhibitors Flashcards

1
Q

What is immunotherapy?

A

a type of biological therapy
a cancer treatment that helps the immune system fight cancer
stimulate immune response
relieve immune inhibition

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2
Q

What is the difference between immunotherapy and other therapies?

A

chemotherapy: targeting fast dividing cells
targeted therapy: targeting a key molecule involved in tumor cell proliferation, growth, survival and/or invasion

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3
Q

What are immune checkpoints?

A

regulators of the immune system
preventing indiscriminative attacking of cells by the immune system
essential for self-tolerance

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4
Q

What are the stimulatory checkpoint molecules?

A

CD28
CD80 (B7-1)
CD86 (B7-2)
4-1BB (CD137)
CD27
CD40

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5
Q

What are the inhibitory checkpoint molecules?

A

CTLA-4 (CD152)
PD-1
B7-H3 (CD276)
B7-H4 (VTCN1)
BTLA (CD272)
KIR

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6
Q

What is the correlation between cancer cells and immune checkpoints?

A

cancer cells can evade immune attacks by stimulating the inhibitory immune checkpoint targets

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7
Q

Describe CTLA-4.

A

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

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8
Q

What happens when CTLA-4 is blocked?

A

stimulate immune system and kill cancer cells

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9
Q

What happens when there is binding between PD-1 and PD-L1?

A

inhibits immune response
-PD-L1 expression helps tumor cells escape the immune system surveillance

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10
Q

What is the target of ipilimumab?

A

CTLA-4

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11
Q

What is the indication for ipilimumab?

A

melanoma
malignant pleural mesothelioma

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12
Q

What is the general tolerance to ipilimumab?

A

better tolerance than chemotherapy

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13
Q

What is the target of tremelimumab?

A

CTLA-4

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14
Q

What is the indication for tremelimumab?

A

hepatocellular carcinoma
metastatic non-small cell lung cancer

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15
Q

What is the target of nivolumab?

A

PD-1

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16
Q

What is the indication for nivolumab?

A

melanoma
malignant pleural mesothelioma
NSCLC
advanced renal cell carcinoma
urothelial carcinoma
classical Hodgkins lymphoma
hepatocellular carcinoma

17
Q

What is the target of pembrolizumab?

A

PD-1

18
Q

What is the indication for pembrolizumab?

A

melanoma
NSCLC
head and neck squamous cell cancer
classical Hodgkins lymphoma
large B-cell lymphoma
urothelial carcinoma
gastric cancer
hepatocellular carcinoma

19
Q

What is the target of cemiplimab?

A

PD-1

20
Q

What is the indication for cemiplimab?

A

metastatic cutaneous squamous cell carcinoma
locally advanced CSCC
limited in “cold” tumors

21
Q

What is the target of atezolizumab?

A

PD-L1

22
Q

What is the indication for atezolizumab?

A

locally advanced or metastatic urothelial carcinoma
metastatic NSCLC
locally advanced or metastatic triple-negative breast cancer

23
Q

What is the target of avelumab?

A

PD-L1

24
Q

What is the indication for avelumab?

A

metastatic Merkel cell carcinoma
metastatic NSCLC
locally advanced or metastatic urothelial carcinoma
advanced renal cell carcinoma

25
Q

What is the target of durvalumab?

A

PD-L1

26
Q

What is the indication for durvalumab?

A

urothelial carcinoma
NSCLC

27
Q

What are the atypical patterns of response?

A

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

28
Q

What are the adverse reactions to immune checkpoint inhibitors?

A

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

29
Q

What is the target of relatimab?

A

LAG-3
-an inhibitory receptor overexpressed in exhausted T cells

30
Q

What is relatimab used in combination with?

A

nivolumab

PHAR211 (16 decks)

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