Biologicals: Role in modern therapeutics

Question 1

What are biologicals

Answer 1

products manufactured from, extracted from, or semi-synthesized from biological products

Question 2

What is recombinant DNA technology?

Answer 2

Insertion of a specific gene from one organism into another.
The bacterial/fungal/animal/human cells act as a factory to produce a particular product (usually protein) expressed by the inserted gene

Question 3

Examples of recombinant DNA technology products

Answer 3

Substances identical (or close to) body’s own signalling molecules
Monoclonal antibodies (mab)
Fusion proteins

Question 4

Chemical mediators

Answer 4

substances involved in cell-to-cell signalling

Question 5

Substances identical (or close to) body’s own signalling molecules examples

Answer 5

(e.g. human insulin, human growth hormone, erythropoietin)

Question 6

Monoclonal antibodies (mab)

Answer 6

Monoclonal antibodies (mab): Similar to human antibodies, described as monoclonal as they are derived from a single cell line (e.g., infliximab, trastuzumab, basiliximab)

Question 7

Fusion proteins

Answer 7

Fusion of two distinct proteins such as a specific receptor with an immunoglobulin examples
(e.g., etanercept, abatacept)

Question 8

what are the 4 chemical mediators

Answer 8

Neurotransmitter
Hormones
Cytokines
Local hormones

Question 9

Humoral immunity

Answer 9

Involves a number of non-specific and immediate defence factors
e.g. surface barriers, complement and the inflammatory response

Question 10

Cellular immunity

Answer 10

Involved with immunological memory
‘adaptive immunity’
e.g. production of antibodies

Question 11

Cytokine

Answer 11

the molecules involved in the communication between immune cells through cell signalling

Question 12

Monoclonal antibody

Answer 12

Monoclonal antibodies are monospecific antibodies made by identical immune cells that are clones of a unique parent cell
Mab’s can selectively and specifically target specific cytokines or cytokine receptors on invading organisms or host cells (including cancer cells)

Question 13

3 types of biologicals being used in NZ

Answer 13

Monoclonal antibodies
Programmed cell death 1 inhibitors (PD1 inhibitors)
Fusion protens

Question 14

Traztuzumab

Answer 14

humanized monoclonal antibody

binds to human epidermal growth factor receptor 2 protein (HER-2) in HER-2 positive tumours in breast cancer

Question 15

Pembrolizumab

Answer 15

Humaized immunoglobulin G4 monoclonal antibody that binds to the programmed cell death receptor (PD1) on T cells
Blocks inhibition of T cell proliferation and cytokine secretion by PD1 - restoring normal immune response to kill tumours

Question 16

Etanercept

Answer 16

TNF receptor fusion protein that binds to and neutralises the pro-inflammatory cytokine tumour necrosis factor-a (TNF-a)
Reduces manifestations of TNF-a over expression, including chronic inflammation and immune system activation

Question 17

Challenges with biologicals

Answer 17

• high molecular weight - must be delivered parenterally
• often high risk of infusion reactions
• expensive to manufacture
• number of cautions and adverse effects
• correct dose and dose schedule is challenging