Biologicals Flashcards
What are biologicals?
Manufactured from, extracted from, or semi-synthesised from biological products e.g. blood products, vaccines, recombinant DNA technology
What is recombinant DNA technology?
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
What is an example of recombinant DNA technology?
Insertion of the human insulin gene into an E.coli strain to produce human insulin
What are some recombinant DNA technology products? How are they classified?
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)
What are chemical mediators?
Substances involved in cell-to-cell signalling are known as chemical mediators
What are the four main groups of chemical mediators?
Neurocrine, endocrine, paracrine & autocrine
What are some examples of chemical mediators?
serotonin, histamine - both neurotransmitters & local hormones
What are the two components of the immune system?
Humoral & cellular
What is humoral component of the immune system?
Humoral immunity involves a number of non-specific & mostly immediate defence factors such as surface barriers, complement & inflammatory response
What is cellular component of the immune system?
Involve with immunological memory for the production of antibodies
How do immune cells communicate?
Cytokines
What is a monoclonal antibody?
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
What was the first MAB produced?
Muronomab (binds to CD3 receptor on T-cells) used to prevent rejection after kidney transplant
What is the original source of suffix omab?
Mouse e.g. murunomab
What is the original source of suffix ximab?
Chimeric e.g. infliximab
What is the original source of suffix zumab?
Humanised e.g. traztumab
What is the original source of suffix umab?
Human e.g. nivolumab
What is Traztuzumab?
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
What is the mechanism of action of Traztuzumab?
It inhibits the proliferation of tumour cells that over express HER-2.
What is the main side-effect of Traztuzumab?
Cardiotoxicity (HER-2 receptors also found on myocardium & cardiac function must be monitored), severe hypersensitivity reaction
What is Pembrolizumab (Keytruda)?
Humanised immunoglobulin G4 MAB that binds to the programmed cell death receptor (PD1) on T-cells
What is the mechanism of action of Pembrolizumab?
This blocks the inhibition of T-cell proliferation and cytokine secretion by PD1, thereby restoring the normal immune response to kill tumour cells.
What are the indication of Prembrolixumab?
Unresectable or metastatic melanoma, advanced or metastatic NSCLC
What are side effects of Prembrolixumab?
Immune-mediated & infusion related reactions, increased risk of rejection of soli organ transplant & of enhanced graft vs host reactions in stem cell transplant
What is Etanercept?
TNF receptor fusion protein that binds to an neutralises the pro-inflammatory cytokine tumour necrosis factor a (THF-a)
What is the mechanism of action of etanercept?
Inhibitor of TNF-a reduces the manifestations of TNF-a over expression, including chronic inflammatory and immune system activation.
What are the indication of etancercept?
Autoimmune conditions such as severe rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, chronic plaque psoriasis
What are the side effects of etancercept?
Worsening of underlying infections, Hep B or C, herpes zoster, TB & blood disorders
Whare are some challenges with biologicals?
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.
