Cancer immunotherapy Flashcards
(48 cards)
How does the immune system target cancer cells?
Cancer down-regulates MHC1 to avoid recognition
Innate cells attack cells with this problem
- during process factors released that kill tumour cells
- innate cells also release cytokines to trigger a response
- APCs alerted
- more innate cells are recruited
- more factors produces
- APCs take cell debris to lymph nodes to trigger adaptive response
- Second wave of immune attack through T cells and B cells/plasma cells
Describe the concept of immunoediting
- Elimination: default setting. Immune system will cut back the tumour
- Equilibrium: immune system is not eradicating the cancer. The cancer is not growing. stage can last decades.
- Escape: The tumour produces a cell that is able to avoid or suppress the immune system. Generates an escape clone that is able to grow unchecked. The tumour will reach a certain size when the immune system will contribute to the cancer rather than just removing it
What are the four approaches to immunotherapy?
- vaccination strategies
- Non-specific therapies
- Antibody therapies
- Cell-based therapies
Describe the vaccination strategy of immunotherapy
You take tumour antigens,
re-vaccinate the patient with it and generate a
stronger immune response and therefore get the
immune system working again.
What are the disadvantages of vaccination immunotherapy
- Requires an intact immune system to work
- They’re generally not very effective
How do non-specific immunotherapies work?
Generate an immune or inflammatory reaction which try to target the cancer non-specifically
What are antibody immunotherapies?
- e.g. monoclonal antibodies
What are cell therapies in immunotherapy?
Taking one or more immune cell components from a patient or donor and using these as the driving
mechanisms for killing the tumour.
What is the idea behind bacterial non-specific immunotherapy?
found that if you injected a mixture of killed bacteria into a tumour, you could stimulate a non-specific inflammatory response that would help to resolve the tumour in many cases.
Name a non-specific immunotherapy and describe how it works
Aldara - a toll-like receptor 8 antagonist
This triggers a non-specific immune response in
humans that drives inflammatory cells to the site.
What are the drawbacks of bacterial-based non-specific immunotherapies
people’s immune systems react in different ways, can
be difficult to gauge the response and dose
accordingly.
What are the non-bacterial non-specific immunotherapies
IL-2 (a T-cell growth factor) for therapy.
Premise: making more T-cells is beneficial
What are the disadvantages of IL-2 therapy?
- Have to be a licensed IL-2 physician, as the
therapeutic window is so narrow - quite a toxic cytokine - as the response can be so
severe - patients kept on a high dependency unit whilst the
medication is administered
How can IL-2 be used to kill target cells?
by tagging a toxin to the end of it and administer it.
This is for cases where the cancer is predominantly
driven by T regulatory cells.
What are T regulatory cells and their role in cancer?
T regulatory cells are an effective method of
suppressing the immune system.
Certain cancers such as renal cell carcinomas actively
recruit T regs into the tumour to protect the tumour
from the immune response.
How is IL-2 used to target T reg cells?
One of the ways this is treated is by targeting the T
regs rather than the tumour.
T regs love IL-2 and suck up huge amounts of it, meaning they will preferentially eat the poisoned IL-2, which
will kill them.
What are conjugate monoclonal antibodies and how are they used in cancer?
Conjugates are also used in cancer. These have a
radioactive tag (radioactive isotope or some sort of
toxin) attached that attack the tumours specifically
with radiation or chemotherapy.
What are the advantages of monoclonal antibody immunotherapies?
These are highly effective in many cases and are used
often. Also are synthetic so can be made very
effectively.
What properties make a cell an appropriate target for monoclonal antibody immunotherapies?
If you have a target that is specific to that cell and nothing else, this has the best outcome as treatment wont
have any knock on effect on other cells.
cancers of the blood, which are disseminated so they are easy to
target with monoclonal antibodies through the peripheral blood or lymph nodes are easier to treat than solid tumours
How can the immune system be targeted with immunotherapies?
Targeting immune system checkpoints to ensure T cells are switched off
What are the T cell checkpoints?
- CTLA-4
- PD-1
What is CTLA-4?
When a T cell is activated, it is a two step process. The T cell receptor and the antigen presenting cell stick
together with the T cell receptor and the antigen. However, this is insufficient to drive a T cell to respond. You
need, whats called a co-stimulatory factor. In most cases, this is CD28, which activates the T cell and causes
them to grow and attack.
You have to be able to switch a T cell off. The innate mechanism for that is by CTLA-4. This binds to the same
molecule that CD28 binds to, B7, and turns T cells back off again.
What is CTLA-4s role in cancer?
CTLA-4 is up-regulated very heavily on T cells by the tumour. It has subverted the immune response,
by turning T cells of when they should be activated.
Why are checkpoint inhibitors used?
If the T cells are switched off, you can’t switch them back on again, unless you have a way of turning off the off switch
