Biologic Drugs Flashcards
What are biologic drugs?
Biologic drugs are large, often protein-based drugs that are similar to, or copies of, entities produced in the body.
Give some examples of biologic drugs.
These include; monoclonal antibodies, recombinant proteins, and vaccines.
What are the characteristics of monoclonal antibodies?
Monoclonal antibodies are tuneable and optimizable like small molecules as well as being highly specific and highly selective. They have a high affinity for their receptors and undergo affinity maturation during the immune response.
What does the monoclonal antibody Adalimumab target?
TNF-alpha.
What is Adalimumab used to treat?
- Rheumatoid arthritis.
- Psoriatic arthritis.
- Ankylosing spondylitis.
- Crohn’s disease.
- Moderate to severe chronic psoriasis.
- Juvenile idiopathic arthritis.
Describe recombinant proteins.
These entities are more diverse structurally and are often natural or mutated human proteins.
Give some examples of recombinant proteins.
Usually cytokines, chemokines, and growth factors.
What does the recombinant protein Etanercept target/how does it work?
It works as a recombinant fusion protein soluble TNF receptor 2 fused to human immunoglobulin G1 Fc.
What is Etanercept used to treat?
- Rheumatoid arthritis.
- Ankylosing spondylosis.
- Juvenile rheumatoid arthritis.
- Plaque psoriasis.
- Psoriatic arthritis.
What is immunogenicity?
Immunogenicity is difficult to define; it may be B-cell and T-cell mediated and is a complex phenomenon. Immunogenicity can be identified experimentally using a battery of methods and can also be predicted through computational techniques.
How can immunogenicity be avoided?
So-called humanised antibodies try to prevent the immune response to mAb. Computational techniques can also be used.
How can biologic drugs be optimised?
Biologic drugs can be optimised using SBDD techniques mediated by protein engineering the affinity and specificity of individual biologics.
They can also be optimised by reducing or abrogating immunogenicity by identifying computationally or mutating experimentally B-cell and T-cell epitopes.
Describe TGN1412 and the cytokine storm that trial volunteers faced when it was administered.
TGN1412 was a humanised mouse antibody which is a superagonist of CD28, a receptor on t-cells. It works by mediating signal 2 activating regulatory T-cells and many other cells.
It was proposed as a treatment for B-cell chronic lymphocytic leukaemia and rheumatoid arthritis. It was developed TeGenero Immuno Therapeutics and went through a phase 1 trial in 2006. This trial was unsuccessful as patients experienced a ‘cytokine storm’ which lead to life-threatening multiple organ failure in 6 healthy volunteers.
