Tumour immunology and immunotherapy of cancer:part 2 Flashcards
What proteins do the vaccines for HPV use?
Structural proteins are used to generate virus particles
How might the tyrosinase enzyme be used in cancer immunotherapy, and what are its side effects
It generally develops poor self-tolerance It is expressed in many melanomas Can direct immune response against it.Local auto-immune depigmentation in melanoma patients
When is p53 considered a tumour-associated antigen and when isit considered a tumour specific antigen?
Tumour-associated antigen – when it is over-expressed Tumour specific antigen – when it becomes mutated
What are tumour-associated antigens?
Tumour-associated antigens (TAA) derive from normal cellular proteins which are aberrantly expressed (timing, location or quantity).
Because they are normal self proteins, for an immune response to occur tolerance may need to be overcome
What are the main problems with the immune surveillance of cancer?
It takes a tumour a while to cause inflammation Antigenic differences between normal and tumour cells can be very subtle
What is immune checkpoint blockade?
- Reduces/removes negative regulatory controls of existing T cell responses - Targets CTLA-4 and PD-1 pathways: - CTLA-4 is expressed on activated and regulatory T cells, binds to CD80/86 (costimulatory molecules on APC) - PD-1 is expressed on activated T cells, binds to PD-L1/L2 (complex expression patterns, may be upregulated on tumours) E.g. Ipilimumab (anti CTLA-4), Nivolumab (anti PD-1), antagonistic antibodies Can be used in a wide variety of cancers
What are the two different times at which vaccines can be given?
Preventative vaccination (before the disease) Therapeutic vaccination (try to control the disease once it has occurred)
What are the requirements for activation of an adaptive anti-cancer immune response?
Local inflammation in the tumour Expression and recognition of tumour antigens
What is the main difference between tumours and viral infections with regards to the immune response?
Viral infections trigger a lot of inflammation, which causes upregulation of costimulatory molecules so an immune response can take place Tumours do not cause very much inflammation, especially early on so they are more likely to be missed by the immune system
Give a few examples of viral infections that can cause cancer inimmunocompetent individuals.
HTLV1 associated leukaemia/lymphoma HepB virus- and HepC virus-associated hepatocellular carcinoma HPV positive genital tumours
What are tumour-associated antigens? Give examples
- Derive from normal cellular proteins which are aberrantly expressed (timing, location or quantity) - Because they are normal self proteins, for an IR to occur, tolerance may need to be overcome E.g. cancer-testes antigens - not expressed in normal adult tissues except male germ cells (some expressed in placenta) E.g. MAGE - melanoma associated antigens - identified in melanoma, also expressed in other tumours E.g. p53 when overexpressed
Give an example of an HPV vaccine.
Gardasil
Describe the problem with tolerance in cancer immunotherapy.
T cells that react strongly with self are deleted (central tolerance) so most people have tolerance against tumour-associated antigens
Explain how breast cancer can lead to the degeneration of the cerebellum.
The antigen that the immune response is directed against is normally expressed in neural tissue It is only expressed in breast tissue when there is a tumour The abnormal expression of this antigen in the breast was noticed and an immune response was mounted, which then also reacted with the normal antigens in the neural tissue –> destruction of purkinje cells in the cerebellum
