Session 4 - Monoclonal Antibodies Flashcards
Describe the structure of the antibody.
Fc region with a hinge to each of the other Fab regions (where the antigen binds). Has a variable region and a hyper variable region.
What is an antigen?
Foreign substance that stimulates antibody production.
What is the epitope?
Region on the the antigen that changes between antigens. Party that binds to the antibody.
What are the 2 major uses of monoclonal antibodies?
Diagnostics
Therapeutics
How are monoclonal antibodies made?
1) immunising a certain species against a specific epitope on an antigen and then harvesting the B lymphocytes from the spleen of the mouse.
2) B lymphocytes then fused with an immortal myeloma cell line not containing any other immunoglobulin producing cells.
3) the resulting hybridoma cells are then cultured in vitro so only the hybridomas survive
4) selected hybridomas are found making a specific desired colonial antibody
Name 2 types of monoclonal antibodies.
Conjugated monoclonal antibodies
Bispecific monoclonal antibodies
How do monoclonal antibodies work?
- binding with cell surface receptors = activate or inhibit cell signalling
- binding = induce cell death
- binding with cell surface receptor = antibody dependent cell mediated cytotoxicity or complement dependent cytotoxicity
- internalisation for antibodies delivering toxins into the cancer cell
- blocking inhibitory effects on T cells. Thus activating T cells to help kill the cancer cells
What are the key cluster of differentiation classifications in haematology?
CD20 - found on middle aged B cells = minimises toxicity as late and early B cells
CD 19 = bispecific A’s also expressed on nervous tissue so not as good as can lead to neurotoxicity
What type of cancer is lymphoma?
- lymphoma divided into B and T cell neoplasms - colonial proliferation of lymphoid cells
- typically causes enlargement of lymph nodes
- the spleen, bone marrow and other areas of the body such as liver, skin, testes and Bowen May also be involved
- people with lymphoma often complain of drenching night sweats, fevers and weight loss. Some will have none of these symptoms
What are the treatment stages in lymphoma?
Chemotherapy Radiotherapy Monoclonal antibody therapy = Rituximab Emerging new targeted therapy Stem cell transplantation
What are the side effects of monoclonal antibodies?
- some have mild or no symptoms e.g. mild fatigue
- many have a mild reaction to the 1st infusion and then tolerate subsequent treatments well
- a few people will have severe infusion related reactions as their immune system reacts to the presence of a foreign protein
How are infusion related reactions (to monoclonal antibodies) managed?
patient education:
- have had pre-med, May still have some side effects
- inform staff the moment of any chnage so staff can take immediate action
- instruct patient to omit their anti-hypertension 12 hrs prior to infusion
Prevention with pre-med = steroid, anti-histamine, paracetamol
Start at a slow infusion rate, slowly increase if tolerated
Drugs required to treat IRRs should be prescribed prior to starting patient’s treatment
Give some examples of monoclonal antibodies used to treat solid cancers.
Trastuzumab = inhibition Of HER2 signalling Bevacizumab = inhibition Of VEG-F signalling Nivolumumab = inhibition Of PD1 signalling
Give some examples of monoclonal antibodies used to treat autoimmune conditions.
Infliximab and Adalimumab = inhibition Of TNF alpha
Give some examples of monoclonal antibodies used to treat cardiology.
Abciximab = inhibition Of platelet glycoprotein IIb/II
