Immune Checkpoint Inhibitors Flashcards
What are some characteristics of immunotherapy?
A type of biological therapy that helps the immune system fight cancer through stimulation
What is an alternate name for CD80?
B7-1
What is an alternate name for CD86?
B7-2
What are some characteristics of immune checkpoints?
- Regulators of the immune system
- Preventing indiscriminative attacking of cells by the immune system
- Essential for self-tolerance
What are some examples of stimulatory immune checkpoint molecules?
- CD28
- CD80
- CD86
- 4-1BB
- CD40
What are some examples of inhibitory checkpoint molecules?
- CTLA-4
- PD-1
How can cancer cells take advantage of inhibitory immune checkpoint molecules?
Cancer cells can evade immune attacks by stimulating the inhibitory immune checkpoint targets
What is CTLA-4?
- Cytotoxic T-lymphocyte-associated protein 4
- Upregulated in T cells upon exposure to antigens
- Inhibitory immune checkpoint (blocking CTLA-4 will stimulate immune system and kill cancer cells)
What is the significance of the PD-1 and PD-L1 interaction?
PD-1 (Programmed cell death protein 1)
PD-L1 (Programmed death-ligand 1)
Binding between PD-1 and PD-L1 inhibits immune response
PD-L1 expression on cancer cells helps them escape immune system surveillance
What are some characteristics of Ipilimumab therapy?
Target: CTLA-4
Indication: Melanoma and malignant pleural mesothelioma
Better tolerated than chemotherapy (but beneficial in only a small portion of patients)
What are some characteristics of Tremelimumab therapy?
Target: CTLA-4
Indication: Hepatocellular carcinoma and Metastatic non-small cell lung cancer
What are some characteristics of Nivolumab therapy?
Target: PD-1
Indication:
- Melanoma
- Malignant pleural mesothelioma
- Non-small cell lung cancer
- Advanced renal cell carcinoma
- Hodgkin’s lymphoma
What are some characteristics of Pembrolizumab therapy?
Target: PD-1
Indication:
- Melanoma
- Non-small cell lung cancer
- Head and neck squamous cell cancer
- Large B-cell lymphoma
What are some characteristics of Cemiplimab therapy?
Target: PD-1
Indicated for metastatic cutaneous squamous cell carcinoma (CSCC)
Limited in use to cold tumours (dense stroma and immunosupressive)
What are some characteristics of Atezolizumab therapy?
Target: PD-L1
Indication:
- Locally advanced or Metastatic urothelial carcinoma
- Metastatic non-small cell lung cancer
- Locally advanced or metastatic triple negative breast cancer (worst prognosis)
What are some characteristics of Avelumab therapy?
Target: PD-L1
Indication:
- Metastatic Merkel cell carcinoma
- Metastatic non-small cell lung cancer
- Locally advanced or metastatic urothelial carcinoma
- Advanced renal cell carcinoma
What are some characteristics of Durvalumab therapy?
Target: PD-L1
Indicated for Urothelial carcinoma and non-small cell lung cancer
What are some common adverse drug reactions associated with immune checkpoint inhibitors?
Rash, diarrhea, and fatigue
What are some rare adverse drug reactions associated with immune check point inhibitors?
Immune-mediated inflammations, such as pneumonitis, hepatitis, nephritis, and colitis
They are all exposed to the environment or have good blood supply and PD-L1 are more common on these tissues and surfaces
What are the two atypical patterns of response to immune checkpoint inhibitors?
- Pseudo-progression
- Hyper-progression
What are some qualities of pseudo-progression pattern of response to immune checkpoint inhibitors?
Immunotherapy does not generate a rapid response (initial increase in volume of cancer lesions due to infiltration of tumoural tissues by immune cells)
What are some qualities of hyper-progression pattern of response to immune checkpoint inhibitors?
Acceleration of tumour growth during imune checpoint inhibition (Tumour adapted to therapy by increasing proliferation, evade detection, and hibernate)
What is an example of a new immune checkpoint inhibitor?
Relatlimab
Target: Lymphocyte activation gene-3 (LAG-3): an inhibitory receptor overexpressed in exhausted T cells
Used in combo with Nivolumab for Melanoma
