Lecture 10 Flashcards
What inside tumour cells can improve people’s diagnosis
Tumour infiltrating lymphocytes
Types of immunotherapy
Immune checkpoint inhibitors: block immune checkpoints e.g. PD1/PDL1 inhibitors or CTLA-4 inhibitors
T-cell transfer therapy - TIL or CAR-T therapy
Monoclonal antibodies
Cancer treatment vaccines
Immune system modulators: cytokines
- Interferons
- Interleukins
Anti-PDL/PDL1 antibodies
Checkpoint inhibitors
Anti-PD1 antibodies bind PD1 on T-cell
Inhibits PDL on tumour cell binding PD1
MHC (tumour cell) and TCR (T-cell) bind antigen
CTLA-4 inhibition
T-cell receptor recognises MHC peptide complex on tumour/dendritic cells
PD-1 on T-cells binds PD-L1, delivering inhibitory signal
CD28 binds B7.1/2 on dendritic cells providing stimulatory signal for T cell activation
CTLA-4 binds B7.1/2 on dendritic cells providing inhibitory signal
Tumours exploit PD-1/PD-L1 interaction to suppress immune responses and escape detection
T-cell transfer therapy
- Uses patient’s own T-cells artificially expanded in lab to kill cancer cells
Two main types:
- Tumor-infiltrating lymphocytes therapy
- CAR-T cell therapy
Involve collecting patient’s T cells, growing them in lab (2-8 weeks) and transferring back to patients
TIL therapy
- TILs found in tumours
- Cells may already be acting against cancer, but may not be in sufficient numbers to have effect
- Lymphocytes tested to identify population that best recognises cancer cells
- Treated with rapid expansion factors
- Injected into patient and attack cancer cells
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CAR-T cell therapy
- Similar to TIL but cells genetically engineered in lab to make them more potent
- Blood removed to get T cells
- CAR-T cells made in lab which express chimetic antigen receptor
- Millions of CAR-T cells made
- CAR-T cells injected back into patient using IV, and CAR-T cells attack cancer cells
Side effects of CAR-T therapy
- Cytokine release syndrome when transferred T cells release large amounts of cytokines
- Causes fever, nausea, headache, rash, rapid heartbeat etc
- Most mild, some life-threatening
- CAR-T sometimes recognises normal cells, leading to potential organ damage
Monoclonal antibodies
- Targets radiotherapies to cancer
- Blocks signalling from receptor tyrosine kinases
- Aid immune system to recognise and destroy cancer cells
Blinatumomab binds CD3 and CD19
Cancer treatment vaccines
Made in three ways
- From patient tumour cells -> cause immune response against specific type of cancer
- Tumour associated antigens found on other cancer cells
- Patient’s dendritic cells - stimulate immune system respond to tumour antigens
Tumour cell based vaccinations
- Immunize mouse with irradiated tumour cells
- Inject viable cells of same tumour -> host response rejects tumor cells and prevents tumor formation
- OR inject viable cells from a second, independently induced tumour -> host response permits proliferation leading to tumour growth
Tumour antigen based
Antigen processed and loaded onto MHC class II on antigen presenting cell surface
Generates antigen specific T-cells
Immune modulating agents
Cytokines:
- Recruit/active immune cells
- Some directly toxic to tumours
- Specific for certain cancer types and cytokines
Interferons:
- INF-alpha - activates dendritic cells and natural killer cells
Interleukins
- IL-2 boosts white blood cell numbers, including cytotoxic T cells and natural killer cells
- Some e.g. IL-7 and IL-15 enhance survival of tumour cells
