Lecture 8 - Flashcards
How do Tumours avoid the anti-tumour immune response?
Can create an immunosuppressive micro environment
Tumour down regulates MHC class I molecules (escaping immune recognition)
Over express inhibitory ligands which inhibit T cells
How do Tumours avoid the anti-tumour immune response?
Can create an immunosuppressive micro environment
Tumour down regulates MHC class I molecules (escaping immune recognition)
Over express inhibitory ligands which inhibit T cells
What is the point of checkpoint inhibitors?
The block the blockers, leading to T cell activationnn adn anti-tumour immune response
What is an example of types of checkpoint inhibitors?
PD1 inhibitors
PDL1 inhibitors
CTLA-4 inhibitors
What is an example of a PD1 inhibitor?
Nivolumab
What are tumour associated antigens?
Normal cell antigens that expresssed on normal tissue but are over expressed
What is an example of a tumour associated antigens?
HER-2 seen in breast cancer
What are tumour specific antigens?
Antigens that are not normally represent in normal healthy tissue
How do we generate chimeric antigen receptor T cells?
Gene for Chimaeriic antigen receptor extracted
Inserted into lentivirus vector
Then gets inserted into a T cell by virus
What receptor do most T cell leukaemia express?
CD7
What are the advantages of bispecific antibodies?
Off the shelf
Access
Favourable toxicity
What are the disadvantages of bispecific antibodies?
Dependant on endogenous T cell function
Durability less clear
Long term administration
What is the benefit of CAR-T over bispecific antibodies?
CAR-T = single infusion
Bispecific =long term
What is cytokine release syndrome?
Where theres T cell expansion and activation due to over activation of the immune system
What are the symptoms of cytokine releases syndrome?
Fever
Chills
Nausea
Vomiting
Diarrhoea
How do you treat cytokine release syndrome?
Steroids
Tociluzumab
What is immune effector cell-associated neurotoxicity syndrome?
Complication of receiving immune CAR-T therapy
Where T cells begin destroying cancer cells and become dysregualated leading to lots of cytokines being releases
Inflammation leading o perturbed blood brain barrier
How is immune effector cell-associated neurotoxicity syndrome treated?
Steroids
What a re the tumour intrinsic reasons why T cell therapies fail?
Target antigen loss
Lineage switching
Loss of CD58
What are the tumour extrinsic reasons why T cell therapies fail?
Limited CAR T-cell expansion
Reduced CAR T-cell persistence
T cell exhaustion/dysfunction
