Targeted Drug Delivery - Cancer 2

Question 1

What does Cetuximab target?

Answer 1

It is an anti-EGFR antibody
It targets the extracellular domain of EGFR, preventing the activation of the receptor and inhibiting cancer cell growth.
Also triggers ADCC where immune cells destroy the cancer cells marked by the antibodies

Question 2

What kind of cancers does Cetuximab treat

Answer 2

Head and neck, colon cancers

Question 3

What are the two major approaches to targeting angiogenesis in cancer?

Answer 3

1. Targeting VEGFR-2 (receptor) to decrease VEGF binding.
2. Targeting VEGF to inhibit its binding to VEGFR-2.

Question 4

What is Bevacizumab (Avastin®)

Answer 4

Bevacizumab is an unconjugated antibody that targets VEGF. It binds to VEGF and sequesters it, preventing it from interacting with VEGFR-2 and blocking angiogenesis.

Question 5

What do HER 1-4 proteins do?

Answer 5

they are receptors for growth regulating ligands, leading to a decrease in apoptosis and an increase in cell proliferation

Question 6

What does HER 2 do?

Answer 6

known to mediate cell signalling pathways

Question 7

What does Trastuzumab target?

Answer 7

It blocks VEGFR 2
Mediator of ADCC (antibody dependent cell mediated cytotoxicity)

Question 8

Name 5 methods of disrupting HER receptor signalling

Answer 8

1. Receptor blocking antibodies
2. Ligand sequestering antibodies
3. Tyrosine kinase inhibitors
4. Antibody-toxin conjugates
5. Inhibitors of downstream signalling molecules

Question 9

What are the two forms of Herceptin®?

Answer 9

IV infusion
SC

Question 10

What special excipient is added to Herceptin?

Answer 10

a-trehalose dihydrate

Question 11

What is important to note during reconstitution of herceptin?

Answer 11

do not shake - AB is sensitive to shear

Question 12

Why should Herceptin not be diluted with glucose solutions?

Answer 12

Can cause aggregation of the protein

Question 13

What is Kadcyla used for?

Answer 13

HER 2 positive breast cancer

Question 14

What are the two main mechanisms of action of Kadcyla?

Answer 14

Suppresses HER2
Releases DM1 (emtansine) into HER2 targeted cells

Question 15

What is the function of the linker in Kadcyla?

Answer 15

The linker connects the antibody to DM1, ensuring a stable bond and preventing the cytotoxic drug from being released until it reaches the targeted cells.

Question 16

Drug + MOA of Kadcyla

Answer 16

DM1 (emtansine) - microtubule inhibitor which disrupts cell division - induces cell cycle arrest and cell death

Question 17

List the 3 elements of an antibody drug conjugate

Answer 17

Antibody that finds CD30 on the surface of target cells
A drug that is designed to cause cell death
A linker that attaches the drug to the antibody

Question 18

What antibody is Mylotarg?

Answer 18

Gemtuzumab ozogamicin

Question 19

What drug is in Mylotarg?

Answer 19

Calicheamicin

Question 20

What is Mylotarg used to treat

Answer 20

Acute myeloid leukemia (AML)

Question 21

What antigen does Gemtuzumab ozogamicin (Mylotarg) target

Answer 21

CD33 antigen on leukemia cells

Question 22

What cytotoxic drug is attached to Gemtuzumab ozogamicin (mylotarg)

Answer 22

Calicheamicin

Question 23

How does Gemtuzumab ozogamicin kill cancer cells?

Answer 23

After internalisation of the CD33 antigen and Gemtuzumab ozogamicin, calicheamicin is released inside lysosomes, binds DNA, causes double-strand breaks, leading to cell death.

Question 24

What is the antibody structure of Gemtuzumab ozogamicin?

Answer 24

A humanized IgG4 kappa antibody with mouse-derived binding regions.

Question 25

What is Adcetris

Answer 25

Brentuximab vedoitin Antibody drug conjugate

Question 26

What does Adcetris treat

Answer 26

Hodgkin lymphoma

Question 27

What are the components of Adcetris?

Answer 27

Antibody: chimeric igg1 antibody (cAC10) targeting CD30 Drug: monomethyl auristatin E (MMAE) - a microtubule disrupting agent LInker - protease cleavable linker - stable outside the cell, cleaved inside

Question 28

What is the drug in Blincyto?

Answer 28

Blinatumomab

Question 29

Indication of Blincyto

Answer 29

Treatment of acute lymphocytic leukemia

Question 30

How does Blinatumomab work?

Answer 30

One part attaches to the CD19 protein, which is found on some leukemia and lymphoma cells. The other part attaches to CD3, a protein found on immune cells and T cells It is a bi-specific antibody

Question 31

What is the drug in Imfinzi

Answer 31

Durvalumab

Question 32

Indication of Imfinzi

Answer 32

Used to treat a type of lung cancer called non-small cell lung cancer (NSCLC)

Question 33

What does Imfinzi (durvalumab) target?

Answer 33

recognises and attaches to a protein called 'programmed death ligand 1' which is present on the surface of many cancer cells + usually switches off immune cells that would otherwise attack the cancer cells

Question 34

What is another name for Imlygic

Answer 34

Talimogene laherparepvec or T-vec

Question 35

What gene does Imlygic carry?

Answer 35

GM-CSF Human granulocyte-macrophage colony-stimulating factor

Question 36

Imlygic is a modified form of which virus

Answer 36

live Herpes simplex type 1 virus

Question 37

MOA of Imlygic

Answer 37

Designed to replicate in cancer cells only. Virus replicates, causing cells to burst open. When they burst, the virus, GM-CSF and tumour fragments are released. GM-CSF helps to attract the immune cells. The immune system then recognises and attacks cancer cells throughout the whole body, not just those where the virus was infected

Question 38

What does CART stand for

Answer 38

Chimeric Antigen Receptor Transduced T cells (CART19 = T cells engineered to express CD19 specific CAR)

Question 39

List 4 drawbacks to CART cells

Answer 39

Cells die Poor lymph homing Limited efficacy in some cases Cost, dedicated facilities, regulatory challenges

Question 40

What are the 3 key components released by the PLG polymer scaffold in in situ therapeutic cancer vaccines

Answer 40

GM-CSF (recruits dendritic cells) CpG-ODN (activates immune cells by mimicking bacterial/viral DNA) Tumor lysate (provides cancer-specific antigens)

Question 41

What is the role of CpG-ODN in cancer vaccines?

Answer 41

CpG-ODN acts as a "danger signal" to activate the immune system by mimicking bacterial and viral DNA.