ADC's and immuno-oncology

Question 1

IgG consist of what?

Answer 1

2 heavy and light chains

Question 2

On mAb’s what are the chains held together by?

Answer 2

Disulfide bond between conserved cysteine residues at the hinge region

Question 3

What region of a mAb binds cell surface Ig receptors?

Answer 3

Fc region

Question 4

Which region of a mAb binds the antigen?

Answer 4

Variable region

Question 5

What is an immuno-conjugate?

Answer 5

An antibody attached to a toxic agent

Question 6

What is an antibody-drug conjugate?

Answer 6

An antibody attached to a small molecule cytotoxic

Question 7

What is the antibody responsible for in a ADC?

Answer 7

Targeting

Question 8

What is the linker responsible for in a ADC?

Answer 8

Release

Question 9

What is the warhead responsible for in a ADC?

Answer 9

Apoptosis

Question 10

What is the advantage of ADCs?

Answer 10

Reduced toxicity

Better tolerated than alternative therapeutically equivalent therapies

Question 11

What do second generation ADCs use?

Answer 11

Drugs 4000 times more toxic

Question 12

What 3 drug classes are favoured for ADCs?

Answer 12

Maytansinoids
Auristatins
Calicheamicins

Question 13

What do maytansinoids do?

Answer 13

Inhibit tubulin reorganisation

Prevent tubulin polymerisation and depolymerisation

Question 14

What do auristatins do?

Answer 14

Inhibit tubulin reorganisation

Prevent tubulin polymerisation only

Question 15

What are two licensed products which are ADCs?

Answer 15

Adcetris

Kadcyla (Trastuzumab emtansine)-HER2

Question 16

T cell activation is initiated by what?

Answer 16

Antigens in combination with major histocompatibility proteins (MHC) on surface of APCs.

Question 17

Ag/MHC binds to wht to propagate intracellular signals in the T cell?

Answer 17

T cell antigen receptor

Question 18

Full T cell activation requires what?

Answer 18

Co-stimulatory signal (CD28 stimulates IL-2)

Question 19

What are immune checkpoints?

Answer 19

They serve to limit T cell activation- blocked by monoclonal antibodies to boost weak anti-tumour responses

Question 20

Cancer cells can over express what?

Answer 20

Inhibitory receptors on their surface

Question 21

What is the aim of immuno-oncology?

Answer 21

To allow T cells to mount an effective immune response against cancer.

Question 22

Name two examples of immune check point receptors

Answer 22

B7——–CTLA-4

cancer cell)PDL1———PD1 (T cell

Question 23

What does ipilimumab target?

Answer 23

CTLA-4