When were MABs discovered and how did it happen
- 1975
- fused mouse myeloma cells with antibody-producing B cells
- created hybrid cells, known as a hybridomas
- produce pure specific antibodies
What are monoclonal antibodies (MABs)
- Designed antibodies that specifically target a certain antigen, such as one found on cancer cells
- highly precise & targeted
- used to treat many diseases
Before the discovery of MABs, what was there
Only polyclonal antibodies of varying speciality
What are the majority of MABs produced by
by Mammalian cell lines, but some produced by bacteria and yeasts
What is the first step in the process of creating MABs
- Immunising an animal (mouse/rabbit) with desired antigen
- The animal’s immune system produces a variety of antibodies in response
What happens after the first step in creating MABs
scientists isolate B-cells from immunised animal, and fuse them with immortal cancer cells, creating hybridomas
how does fusion of cancer cells and B cells occur
using electrofusion or chemical fusion techniques (such as polyethylene glycol)
what are antibodies
highly complex molecules, with extremely specific folding crucial to their function
what are the 4 types of MAB
murine
chimeric
humanised
fully human
murine MABs
- fully derived from mice
- hybridomas created by fusing mouse B cells with cancer cells
- highly effective, but may induce an immune response in humans due to foreign origin
- ‘omab’
what do the cancer cells that are fused with hybridomas provide
stable environment for hybridomas to produce desired MABs
chimeric MABs
- lower chance of immune response
- 50% human constant region, responsible for immune system activation
- 50% mouse variable region, that recognises specific targets
- ‘ximab’
humanised MABs
- ~90% human, with complementary determining regions
- smaller mice portion undergoes genetic modifications, making it more similar to human antibodies
- decreased risk of immune response
- ‘zumab’
fully human MABs
- derived only from human sequences
- can be generated using advanced techniques like phage display or transgenic animals
- have lowest risk of immune response
- typically very well tolerated in body
- ‘umab’
what various factors does selection of MAB depend on
- therapeutic purpose
- efficacy
- safety considerations
other types of MAB (specialised)
- naked
- bispecific
- conjugated antibodies
naked antibodies
- unmodified
- exert their therapeutic effect by binding and mediating immune response OR disrupt signalling pathways
bispecific MABs
- engineered to have 2 targets
- therapeutic effect comes from bringing together their target (cancer/virus) cells and immune cells
conjugated MABs
- processed to be conjugated to another molecule, such as fluorescent dye or drug
- conjugated antibody targets a specific molecule/cell in body/sample
- when conjugated to drug, can deliver targeted therapy to specific cells such as cancer
what is a magical bullet
a term used to describe a hypothetical, ideal drug/treatment that specifically targets and eliminates a disease, without harming healthy cells
what is the significant role played by MABs in the development of magic bullets
- they can be engineered to recognise & bind to specific molecules or cells
- have potential to deliver targeted therapies to desired site, e.g. cancer cells
why is the specificity of MABs so important
- reduces risk of harmful side-effects
- increases effectiveness of treatment
