Cancer Therapy: Immune Checkpoint Inhibitors

Question 1

What is immunotherapy? (4)

Answer 1

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

Question 2

How does chemotherapy differ from immunotherapy?

Answer 2

Chemotherapy targets fast dividing cells

Question 3

How does targeted therapy differ from immunotherapy?

Answer 3

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

Question 4

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

Answer 4

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

Question 5

What are some stimulatory checkpoint molecules? (6)

Answer 5

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

Question 6

What are some inhibitory checkpoint molecules? (6)

Answer 6

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

Question 7

How can cancer cells evade immune attacks via immune checkpoints?

Answer 7

Cancer cells stimuate the inhibitory immune checkpoint targets

Question 8

How does CTLA-4 work? (3)

Answer 8

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)

Question 9

CTLA-4 has ______ binding affinity than CD28

Answer 9

higher

Question 10

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

Answer 10

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

Question 11

Blocking CTLA-4 results in what?

Answer 11

Stimulates immune system and kills cancer cells

Question 12

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

Answer 12

inhibits

Question 13

PD-L1 expression allows tumors cells to do what?

Answer 13

Helps tumor cells escape the immune system surveillance

Question 14

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

Answer 14

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

Question 15

What does Tremelimumab target?

Answer 15

CTLA-4

Question 16

What are the indications for tremelimumab? (2)

Answer 16

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

Question 17

What does Nivolumab target?

Answer 17

PD-1

Question 18

What are the indications for nivolumab? (7)

Answer 18

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

Question 19

What does pembrolizumab target?

Answer 19

PD-1

Question 20

What are the indications for pembrolizumab? (8)

Answer 20

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

Question 21

What does cemiplimab target?

Answer 21

PD-1

Question 22

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

Answer 22

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

Question 23

What does atezolizumab target?

Answer 23

PD-L1

Question 24

What are the indications for atezolizumab? (3)

Answer 24

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

Question 25

What does avelumab target?

Answer 25

PD-L1

Question 26

What are the indications for avelumab? (4)

Answer 26

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

Question 27

What does durvalumab target?

Answer 27

PD-L1

Question 28

What are the indications for durvalumab? (2)

Answer 28

1. Urothelial carcinoma 2. NSCLC

Question 29

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

Answer 29

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

Question 30

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

Answer 30

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

Question 31

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

Answer 31

1. Rash 2. Diarrhea 3. Fatigue

Question 32

What does relatlimab target? (2)

Answer 32

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

Question 33

What is the indication for relatlimab?

Answer 33

Melanoma