What is a monoclonal antibody and what can they be used for?
Monovalent antibodies which bind to the same epitope and are produced by a single B-lymphocyte clone
Used for diagnosis (e.g pregnancy, ABO) and therapeutics (e.g cancer treatment)
What is the original method for producing monoclonal antibodies?
Immunise a species against a specific epitope on an antigen and then harvest the B-lympocytes from the spleen of the mouse
Fuse the B-lymphocytes with an immortal myeloma cell line and then culture the hybridoma cells in vitro so only the hybridoma cells survive
Selected hybridomas are found making the specific desired clonal antibody
What are the different types of monoclonal antibody and how are they named?
As the go along to human they get longer half lifes as they are under less immune attack
What are conjugated monoclonal antibodies?
ADC - Antibody Drug Complex
They are an antibody with a radioactive or chemotherapy particle attached to them so they can selective kill cells
Sometimes get internalised by endocytosis into the cell and cause cell lysis
What are bispecific monoclonal antibodies?
The double binding activates the T cell so it can kill the other cell attached to the antibody, e.g by perforins and granzymes
Often uses anti-CD3
How do monoclonal antibodies work as an anti-cancer drug? (multiple mechanisms)
ADCC: Antibody dependent cell mediatied cytotoxicity
CDC: complement dependent cytotoxicity
- Bind with cell surface receptors and either activate or inhibit signally or can induce cell death
- Can be internalised into the cell and the antibodies can deliver the toxins
- Can block T cell checkpoints so T cells are activated for longer so can kill more cancer cells
What are some antigens used to make monoclonal antibodies?
What type of cancer is lymphoma?
- Lymphoid cells (T and B cells)
- Causes enlargement of lymph nodes but can also involve the spleen, bone marrow, liver, skin, testes and bowel
- Can cause B symptoms such as weight loss and drenching night sweats
What antigen do B-cell lymphomas normally express?
CD20 so use Rituximab as this is an anti-CD20 antibody
What are the treatment strategies for lymphoma?
- Monoclonal antibody therapy
- Radiotherapy (if bulky or in one place)
- Stem cell transplantation
What are the side effects associated with monoclonal antibodies?
- Often no or mild symptoms e.g fatigue
- Infusion related reactions (often on 1st infusion but then tolerate further treatments)
How can we manage/prevent infusion related reactions associated with monoclonal antibodies?
- Patient education: warn patient they may experience side effects, tell them to stop antihypertensives 12 hours before infusion, tell them to inform staff the moment of any changes
- Prevent with premeds: steroids, antihistamines, paracetamol
- Slow infusion rate and slowly increase if tolerated
- Prescribe drugs to treat reaction before administering the monoclonal antibody
Give some examples of monoclonal antibodies and how they work.