Immunotherapy 2 Flashcards
Mechanism of immune checkpoint protein inhibition
1) co-stimulation i CD28 ligation trances T cell activating signs (when presented to MHC on APC)
2) CTLA-4 ligaton on activated T cell down-regulates T cell responses
3) blocking CTLA-4 legation enhances T cell response
when CTLA-4 on T cell binds B7 on APC
no cell activation
When anti-CTLA4 mAB blocks CTLA-4 from binding to B7
T cell activation
example of an immune checkpoint proteins
CTLA4- keeps immune responses in check by preventing overly intense responses that might damage normal cells
first drug used to modulate checkpoint proteins in immune response
Ipilimumab - treatment of advanced melanoma- blocks activity of CTLA4
what activity does Ipilimumab block
CTLA4- means cannot complex with B7 on APC- enhancing T cell activation
Immune Checkpoint Protein Inhibition Therapy
- Nivolumab
approved for patients with advanced melanoma or advanced lung cancer
Immune Checkpoint Protein Inhibition Therapy
- pembrolizumab
approved for patients with advanced melanoma
TGN1412 is called
Theralizumab
TGN1412 was used as an
immuno-modulaotry frug for rheumatoid arthritiis
how did TGN1412 work
binds to CD28 co-stimualtor pair on T cells
- potent agonist
- stimulation inflammatory production
-causes severe inflammatory reaction due to CYTOKINE RELEASE SYNDROME
Adoptive Immune cell therapy: Normal TILs
Idea behind this approach is that the TILs have already shown the ability to target tumor cells, but there may not be enough of them within the tumour to eradicate it or overcome the immune suppressive signals that are being released there
Introducing massive amounts of activated TILs can help to overcome these barriers and shrink or destroy tumors
In some experimental cases these treatment responses
have lasted for years
process of using normal TILs to treat tumour cells
- TILs are collected from samples of the tumour
- TILS that show the greatest recognition of the patients tumour in lab are selected
- cells are then activated with cytokines and unfused into the patients blood stream
Transgenic TILs
T cells are engineered to have a specific transgenic TCR which we know has high affinity to a certain tumour antigen
CAR-T Cells
Chimeric Antigen Receptor Modified T cells