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PHAR 211 > Cancer Therapy: Immune Checkpoint Inhibitors > Flashcards

Cancer Therapy: Immune Checkpoint Inhibitors Flashcards

1
Q

What is immunotherapy? (4)

A
  1. A type of biological therapy
  2. A cancer treatment that helps the immune system fight cancer
  3. Stimulate immune responses
  4. Relieve immune inhibition
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2
Q

How does chemotherapy differ from immunotherapy?

A

Chemotherapy targets fast dividing cells

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3
Q

How does targeted therapy differ from immunotherapy?

A

Targeted therapy targets a key molecule involved in tumor cell proliferation, growth, survival, and/or invasion

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4
Q

What are immune checkpoints? (3) (What is their purpose?)

A
  1. Regulators of the immune system
  2. Preventing indiscriminative attacking of cells by the immune system
  3. Essential for self-tolerance
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5
Q

What are some stimulatory checkpoint molecules? (6)

A
  1. CD28
  2. CD80 (B7-1)
  3. CD86 (B7-2)
  4. 4-1BB (CD137)
  5. CD27
  6. CD40
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6
Q

What are some inhibitory checkpoint molecules? (6)

A
  1. CTLA-4 (CD152)*
  2. PD-1*
  3. B7-H3 (CD276)
  4. B7-H4 (VTCN1)
  5. BTLA (CD272)
  6. KIR
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7
Q

How can cancer cells evade immune attacks via immune checkpoints?

A

Cancer cells stimuate the inhibitory immune checkpoint targets

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8
Q

How does CTLA-4 work? (3)

A
  1. Upregulated in T cells upon exposure to antigens
  2. Checkpoint molecule that inhibits immune responses
  3. Binding B7-1 (CD80) or B7-2 (CD86)
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9
Q

CTLA-4 has ______ binding affinity than CD28

A

higher

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10
Q

Compare CTLA-4 and CD28 in terms of abundance, affinity, and where they’re expressed.

A
  1. CTLA-4 - low abundance and high affinity, not expressed by resting T cells
  2. CD28 - high abundance and low affinity, expressing constitutively in T cells
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11
Q

Blocking CTLA-4 results in what?

A

Stimulates immune system and kills cancer cells

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12
Q

Binding between PD-1 and PD-L1 ________ immune response

A

inhibits

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13
Q

PD-L1 expression allows tumors cells to do what?

A

Helps tumor cells escape the immune system surveillance

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14
Q

List some of the FDA approved immune checkpoint inhibitors (8)

A
  1. Ipilimumab
  2. Tremelimumab
  3. Nivolumab
  4. Pembrolizumab
  5. Cemiplimab
  6. Atezolizumab
  7. Avelumab
  8. Durvalumab
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15
Q

What does Tremelimumab target?

A

CTLA-4

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16
Q

What are the indications for tremelimumab? (2)

A
  1. Hepatocellular carcinoma (in combination with durvalumab)
  2. Metastatic non-small cell lung cancer (NSCLC) (in combination with durvalumab and platinum-based chemotherapy)
17
Q

What does Nivolumab target?

A

PD-1

18
Q

What are the indications for nivolumab? (7)

A
  1. Melanoma
  2. Malignant pleural mesothelioma (in combination with ipilimumab)
  3. NSCLC (3 mg/kg nivolumab + 1 mg/kg ipilimumab)
  4. Advanced renal cell carcinoma
  5. Urothelial carcinoma
  6. Classical Hodgkin’s lymphoma
  7. Hepatocellular carcinoma
19
Q

What does pembrolizumab target?

A

PD-1

20
Q

What are the indications for pembrolizumab? (8)

A
  1. Melanoma
  2. NSCLC
  3. Head and neck squamous cell cancer
  4. Classical Hodgkin’s lymphoma
  5. Large B-cell lymphoma
  6. Urothelial carcinoma
  7. Gastric cancer
  8. Hepatocellular carcinoma
21
Q

What does cemiplimab target?

A

PD-1

22
Q

What are the indications of cemiplimab? (2 + 1)

A
  1. Metastatic cutaneous squamous cell carcinoma (CSCC)
  2. Locally advanced CSCC
  3. Limited in “cold” tumors (“cold”: dense stroma and
    immunosuppressive in TMEs)
23
Q

What does atezolizumab target?

A

PD-L1

24
Q

What are the indications for atezolizumab? (3)

A
  1. Locally advanced or metastatic urothelial carcinoma
  2. Metastatic NSCLC
  3. Locally advanced or metastatic triple-negative breast cancer
25
Q

What does avelumab target?

A

PD-L1

26
Q

What are the indications for avelumab? (4)

A
  1. Metastatic Merkel cell carcinoma (MCC)
  2. Metastatic NSCLC
  3. Locally advanced or metastatic urothelial carcinoma
  4. Advanced renal cell carcinoma
27
Q

What does durvalumab target?

A

PD-L1

28
Q

What are the indications for durvalumab? (2)

A
  1. Urothelial carcinoma
  2. NSCLC
29
Q

Atypical patterns of response includes pseudo-progression and hyper-progression. What is pseudo-progression? (3)

A
  1. A response to treatment after initial increase in volume of cancer lesions, due to the infiltration of tumoral tissue by immune cells
  2. Immunotherapy does not generate a rapid response
  3. Response to treatment, when obtained, will last over time due to the immunological memory
30
Q

Atypical patterns of response includes pseudo-progression and hyper-progression. What is hyper-progression? (2)

A
  1. Acceleration of tumor growth during immune checkpoint inhibition
  2. Incidence rate: 4% to 29%
31
Q

What are the most common ADRs associated with immune checkpoint inhibitors? (3)

A
  1. Rash
  2. Diarrhea
  3. Fatigue
32
Q

What does relatlimab target? (2)

A
  • Lymphocyte activation gene-3 (LAG-3 or CD223) - an inhibitory receptor overexpressed in exhausted T cells
  • Ligands: MHC-II and fibrinogen family protein FGL1
33
Q

What is the indication for relatlimab?

A

Melanoma

PHAR 211 (10 decks)

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