Intro to Immunotherapy Flashcards
Cancer Immunity
Cancer can express cancer-specific proteins called neoantigens
Neoantigens can be targeted by:
T cells
What are Neoantigens?
cancer-specific proteins
Cancer immunotherapy examples:
- ) Checkpoint inhibitors
- ) Adoptive cell transfer
- ) Therapeutic vaccines
What are the ways that cancer “evades” ?
- ) Escape immune detection
2. ) Suppress anti-tumor responses
Escape immune detection
by adopting certain features like loss of cell surface antigens.
suppress anti-tumor responses
by activating immune regulatory pathways that inhibit T-cell activity.
what’s a checkpoint inhibitor?
Targeted antibodies that reactivate anti-cancer immune responses by releasing the brakes on the immune system.
what is a CAR (T cell)?
Chimeric antigen receptor
What do they do?
They are T-cells that are re-engineered to express receptors that specifically recognize cancer cells.
What are TIL’s?
Tumor-infiltrating lymphocytes
What do they do?
cultured to produce large quantities of activated T cells that will re-infiltrate the tumor, recognize the cancer cells and destroy them.
What does our immune system do? if working properly?
instructs the body to elicit immune responses to fight pathogens and promote health and well-being.
Cancer cells can evade (escape) elimination by:
- escaping immune surveillance mechanisms
- suppressing anti-cancer responses
Cancer immunotherapy eliminates cancer indirectly by promoting what?
anti-cancer immune responses (stimulates T cell activation and detection of cancer antigens)
What are the 3 types of immunotherapies that stimulate T cell reactivity against cancer?
1) checkpoint inhibitors
2) adoptive T cell transfers
3) cancer vaccines
What’s the goal with fighting cancer in the body?
For the T-cell to recognize the antigen
What is PD-L1 and PD-1?
Proteins that recognize and bind to each other.
What does the PD-L1 inhibitor do?
it makes the T-cell able to recognize the antigen and kill the tumor cell (cancer).
How is the presence of PD-L1 determined on the tumor?
Immunohistochemistry. (IHC) looking for proteins on the tumor.
Facts about the inhibitors
- checkpoint inhibitor drugs, line of immunotherapy
- multiple inhibitors have FDA approval for a variety of applications
What is the most studied and best known PD-1 inhibitor?
pembrolizumab (Keytruda)
What are PD-L1 clones?
nearly identical antibodies that come from different cell lines. Different but function the same way.
What is the hottest immunotherapy marker right now?
TMB*
3 biggest immunotherapy markers
- MSI
- TMB
- PD-L1
Describe what is meant by PD-L1 clone?
almost identical antibodies but slightly different than each other. Because of this, you have to run different immunotherapies.
The clinician needs to know which clone they are wanting to oder. True or false?
True
Tempus has a default clone that we offer? True or false
True
Which immunotherapy metric other than PD-L1 is analyzed at Tempus using IHC?
mismatched repair deficiency
Why is tumor mutational burden (TMB) an indicator for immunotherapy?
they make it easier for the immune system to recognize a cancer cell
Why is MSI an indicator for immunotherapy ?
they make it easier for the immune system to recognize a cancer cell.
More neoantigens produced by tumor=higher chance cancer cells will be recognized and killed by immune cells? true or false?
True
Tumor mutational burden
a proxy for neoantigen production
Measuring microsatelllite instability
We are trying to see how many error-prone areas are in a cell.
Different microsatellite instability
- ) MSI-H
- ) MSS
- ) MSE
Microsatellite Instability- High (MSI-H)
a number of microsatellites in tumor cells is significantly different than the number of repeats in the DNA of a normal cell.
Microsatellite Stable (MSS)
number of microsatellites in tumor cells is not significantly different than the number of repeats in the DNA of a normal cell.
Microsatellite Equivocal (MSE)
tumor cannot be classified as either MSI-H or MSS based on test values.
