ADC's and immuno-oncology Flashcards
IgG consist of what?
2 heavy and light chains
On mAb’s what are the chains held together by?
Disulfide bond between conserved cysteine residues at the hinge region
What region of a mAb binds cell surface Ig receptors?
Fc region
Which region of a mAb binds the antigen?
Variable region
What is an immuno-conjugate?
An antibody attached to a toxic agent
What is an antibody-drug conjugate?
An antibody attached to a small molecule cytotoxic
What is the antibody responsible for in a ADC?
Targeting
What is the linker responsible for in a ADC?
Release
What is the warhead responsible for in a ADC?
Apoptosis
What is the advantage of ADCs?
Reduced toxicity
Better tolerated than alternative therapeutically equivalent therapies
What do second generation ADCs use?
Drugs 4000 times more toxic
What 3 drug classes are favoured for ADCs?
Maytansinoids
Auristatins
Calicheamicins
What do maytansinoids do?
Inhibit tubulin reorganisation
Prevent tubulin polymerisation and depolymerisation
What do auristatins do?
Inhibit tubulin reorganisation
Prevent tubulin polymerisation only
What are two licensed products which are ADCs?
Adcetris
Kadcyla (Trastuzumab emtansine)-HER2
T cell activation is initiated by what?
Antigens in combination with major histocompatibility proteins (MHC) on surface of APCs.
Ag/MHC binds to wht to propagate intracellular signals in the T cell?
T cell antigen receptor
Full T cell activation requires what?
Co-stimulatory signal (CD28 stimulates IL-2)
What are immune checkpoints?
They serve to limit T cell activation- blocked by monoclonal antibodies to boost weak anti-tumour responses
Cancer cells can over express what?
Inhibitory receptors on their surface
What is the aim of immuno-oncology?
To allow T cells to mount an effective immune response against cancer.
Name two examples of immune check point receptors
B7——–CTLA-4
cancer cell)PDL1———PD1 (T cell
What does ipilimumab target?
CTLA-4
