Biologicals

Question 1

What are biologicals?

Answer 1

Manufactured from, extracted from, or semi-synthesised from biological products e.g. blood products, vaccines, recombinant DNA technology

Question 2

What is recombinant DNA technology?

Answer 2

Involves insertion (splicing) of a specific gene from one organism into another (sometimes called genetic engineering)
The bacterial/fungal/animal/human cells act as a 'factory' to produce a particular product (usually a protein) expressed by the inserted gene

Question 3

What is an example of recombinant DNA technology?

Answer 3

Insertion of the human insulin gene into an E.coli strain to produce human insulin

Question 4

What are some recombinant DNA technology products? How are they classified?

Answer 4

Substances identical (or close to) body’s own signalling molecules (e.g. insulin, HGH, erythropoietin)
Monoclonal antibodies: similar to human antibodies, described as monoclonal as they are derived from a single cell line (e.g. infliximab)
Fusion proteins: fusion of two distinct proteins such as a specific receptor with an immunoglobulin (e.g. entanercept, abatacept)

Question 5

What are chemical mediators?

Answer 5

Substances involved in cell-to-cell signalling are known as chemical mediators

Question 6

What are the four main groups of chemical mediators?

Answer 6

Neurocrine, endocrine, paracrine & autocrine

Question 7

What are some examples of chemical mediators?

Answer 7

serotonin, histamine - both neurotransmitters & local hormones

Question 8

What are the two components of the immune system?

Answer 8

Humoral & cellular

Question 9

What is humoral component of the immune system?

Answer 9

Humoral immunity involves a number of non-specific & mostly immediate defence factors such as surface barriers, complement & inflammatory response

Question 10

What is cellular component of the immune system?

Answer 10

Involve with immunological memory for the production of antibodies

Question 11

How do immune cells communicate?

Answer 11

Cytokines

Question 12

What is a monoclonal antibody?

Answer 12

Are monospecific antibodies made by identical immune cells that are clones of a unique parent cell
Mabs can selectively & specifically target specific cytokines or cytokine receptors on invading organisms or host cells
Sometimes called immunomodulators

Question 13

What was the first MAB produced?

Answer 13

Muronomab (binds to CD3 receptor on T-cells) used to prevent rejection after kidney transplant

Question 14

What is the original source of suffix omab?

Answer 14

Mouse e.g. murunomab

Question 15

What is the original source of suffix ximab?

Answer 15

Chimeric e.g. infliximab

Question 16

What is the original source of suffix zumab?

Answer 16

Humanised e.g. traztumab

Question 17

What is the original source of suffix umab?

Answer 17

Human e.g. nivolumab

Question 18

What is Traztuzumab?

Answer 18

Humanised MAB that binds to the human epidermal growth factor receptor 2 protein (HER-2) in HER-2 positive tumours in patients with breast cancer

Question 19

What is the mechanism of action of Traztuzumab?

Answer 19

It inhibits the proliferation of tumour cells that over express HER-2.

Question 20

What is the main side-effect of Traztuzumab?

Answer 20

Cardiotoxicity (HER-2 receptors also found on myocardium & cardiac function must be monitored), severe hypersensitivity reaction

Question 21

What is Pembrolizumab (Keytruda)?

Answer 21

Humanised immunoglobulin G4 MAB that binds to the programmed cell death receptor (PD1) on T-cells

Question 22

What is the mechanism of action of Pembrolizumab?

Answer 22

This blocks the inhibition of T-cell proliferation and cytokine secretion by PD1, thereby restoring the normal immune response to kill tumour cells.

Question 23

What are the indication of Prembrolixumab?

Answer 23

Unresectable or metastatic melanoma, advanced or metastatic NSCLC

Question 24

What are side effects of Prembrolixumab?

Answer 24

Immune-mediated & infusion related reactions, increased risk of rejection of soli organ transplant & of enhanced graft vs host reactions in stem cell transplant

Question 25

What is Etanercept?

Answer 25

TNF receptor fusion protein that binds to an neutralises the pro-inflammatory cytokine tumour necrosis factor a (THF-a)

Question 26

What is the mechanism of action of etanercept?

Answer 26

Inhibitor of TNF-a reduces the manifestations of TNF-a over expression, including chronic inflammatory and immune system activation.

Question 27

What are the indication of etancercept?

Answer 27

Autoimmune conditions such as severe rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, chronic plaque psoriasis

Question 28

What are the side effects of etancercept?

Answer 28

Worsening of underlying infections, Hep B or C, herpes zoster, TB & blood disorders

Question 29

Whare are some challenges with biologicals?

Answer 29

The chemical nature of biologicals is that they are complex proteins with a high molecular weight. this renders them unsuitable for oral delivery & need to be administered parenterally.
They are technically very difficulty (& expensive) to manufacture in large quantities.
Innovator companies will seek to recoup their very expensive research & development costs while they are patent.