Cancer Therapy: Immune Checkpoint Inhibitors Flashcards
What is immunotherapy? (4)
- A type of biological therapy
- A cancer treatment that helps the immune system fight cancer
- Stimulate immune responses
- Relieve immune inhibition
How does chemotherapy differ from immunotherapy?
Chemotherapy targets fast dividing cells
How does targeted therapy differ from immunotherapy?
Targeted therapy targets a key molecule involved in tumor cell proliferation, growth, survival, and/or invasion
What are immune checkpoints? (3) (What is their purpose?)
- Regulators of the immune system
- Preventing indiscriminative attacking of cells by the immune system
- Essential for self-tolerance
What are some stimulatory checkpoint molecules? (6)
- CD28
- CD80 (B7-1)
- CD86 (B7-2)
- 4-1BB (CD137)
- CD27
- CD40
What are some inhibitory checkpoint molecules? (6)
- CTLA-4 (CD152)*
- PD-1*
- B7-H3 (CD276)
- B7-H4 (VTCN1)
- BTLA (CD272)
- KIR
How can cancer cells evade immune attacks via immune checkpoints?
Cancer cells stimuate the inhibitory immune checkpoint targets
How does CTLA-4 work? (3)
- Upregulated in T cells upon exposure to antigens
- Checkpoint molecule that inhibits immune responses
- Binding B7-1 (CD80) or B7-2 (CD86)
CTLA-4 has ______ binding affinity than CD28
higher
Compare CTLA-4 and CD28 in terms of abundance, affinity, and where they’re expressed.
- CTLA-4 - low abundance and high affinity, not expressed by resting T cells
- CD28 - high abundance and low affinity, expressing constitutively in T cells
Blocking CTLA-4 results in what?
Stimulates immune system and kills cancer cells
Binding between PD-1 and PD-L1 ________ immune response
inhibits
PD-L1 expression allows tumors cells to do what?
Helps tumor cells escape the immune system surveillance
List some of the FDA approved immune checkpoint inhibitors (8)
- Ipilimumab
- Tremelimumab
- Nivolumab
- Pembrolizumab
- Cemiplimab
- Atezolizumab
- Avelumab
- Durvalumab
What does Tremelimumab target?
CTLA-4
What are the indications for tremelimumab? (2)
- Hepatocellular carcinoma (in combination with durvalumab)
- Metastatic non-small cell lung cancer (NSCLC) (in combination with durvalumab and platinum-based chemotherapy)
What does Nivolumab target?
PD-1
What are the indications for nivolumab? (7)
- Melanoma
- Malignant pleural mesothelioma (in combination with ipilimumab)
- NSCLC (3 mg/kg nivolumab + 1 mg/kg ipilimumab)
- Advanced renal cell carcinoma
- Urothelial carcinoma
- Classical Hodgkin’s lymphoma
- Hepatocellular carcinoma
What does pembrolizumab target?
PD-1
What are the indications for pembrolizumab? (8)
- Melanoma
- NSCLC
- Head and neck squamous cell cancer
- Classical Hodgkin’s lymphoma
- Large B-cell lymphoma
- Urothelial carcinoma
- Gastric cancer
- Hepatocellular carcinoma
What does cemiplimab target?
PD-1
What are the indications of cemiplimab? (2 + 1)
- Metastatic cutaneous squamous cell carcinoma (CSCC)
- Locally advanced CSCC
- Limited in “cold” tumors (“cold”: dense stroma and
immunosuppressive in TMEs)
What does atezolizumab target?
PD-L1
What are the indications for atezolizumab? (3)
- Locally advanced or metastatic urothelial carcinoma
- Metastatic NSCLC
- Locally advanced or metastatic triple-negative breast cancer
What does avelumab target?
PD-L1
What are the indications for avelumab? (4)
- Metastatic Merkel cell carcinoma (MCC)
- Metastatic NSCLC
- Locally advanced or metastatic urothelial carcinoma
- Advanced renal cell carcinoma
What does durvalumab target?
PD-L1
What are the indications for durvalumab? (2)
- Urothelial carcinoma
- NSCLC
Atypical patterns of response includes pseudo-progression and hyper-progression. What is pseudo-progression? (3)
- A response to treatment after initial increase in volume of cancer lesions, due to the infiltration of tumoral tissue by immune cells
- Immunotherapy does not generate a rapid response
- Response to treatment, when obtained, will last over time due to the immunological memory
Atypical patterns of response includes pseudo-progression and hyper-progression. What is hyper-progression? (2)
- Acceleration of tumor growth during immune checkpoint inhibition
- Incidence rate: 4% to 29%
What are the most common ADRs associated with immune checkpoint inhibitors? (3)
- Rash
- Diarrhea
- Fatigue
What does relatlimab target? (2)
- Lymphocyte activation gene-3 (LAG-3 or CD223) - an inhibitory receptor overexpressed in exhausted T cells
- Ligands: MHC-II and fibrinogen family protein FGL1
What is the indication for relatlimab?
Melanoma
