Monoclonal Antibodies Flashcards
What is a monoclonal antibody and what is it made up of?
Monoclonal - recognise one specific antigen
Antibody - immunoglobulin secreted by beta cells.
Monovalent antibodies which bind to the same epitope and are produced from a single B- lymphocyte clone
Variable region of heavy chain and variable region of light chain, Hypervariable regions, antibody binding fragment, crystallisable fragment (binds to immune- effector cells)
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How do you create monoclonal antibodies?
Through the generation of hybridomas:
- immunising a certain species against a specific epitope on an antigen
- harvesting the B-lymphocytes from the spleen of the mouse
- B lymphocytes fused with immortal myeloma cell line
- Hybridoma cells are culture in vitro
- Selected hybridomas make a specific desired colonal antibody
Uses of monoclonal antibodies
Pregnancy tests
Cancer diagnosis
Cancer treatment
Locating clots
Detect hormones in blood
Diagnoses HIV/ herpes/ chlamydia
Types of monoclonal antibodies
Naked - can now be 100% human through transgenic mice with a human gene
Conjugated - linker and drug
Bispecific - simultaneously binds two antigen types e.g. binds B and T cells to kill B cells
How do conjugated MCABs work?
Antibody has a stable linker which binds to a drug
The antibody can bind to cancer cell antigens so the cytotoxic drug only kills the bound cancerous cells
The stable linker means it’s inactive while circulating
May: prevent signalling, antibody dependent cytotoxicity, induce apoptosis
How do bispsecific monoclonal antibodies work?
Antibody one arm bind B cell and one arm to T cell -> once both arms engaged the T cell is activated and kills B cell (apoptosis)
E.g. for B cell lymphomas
How do mononoclonal antibodies work?
Binding cell surface receptors -> activate/ inhibit signalling within the cell OR induce cell death OR active AB-dependent cell-mediated cytotoxicity/ complement- dependent cytotoxicity
Internalisation if delivering toxins into cancer cell
Blocking inhibitory effects on T cells (checkpoints) -> activated to help kill cancer cells
What is lymphoma?
Cancer of the blood - either B or T cell neoplasms - enlargement LNs - also may involve spleen, BM, liver, skin, testes, bowel - night sweats, fevers, weight loss common
LN taken over by small clonal B lymphocytes which retain follicular pattern = follicular lymphoma
OR
By larger clonal B lymphocytes take over node in diffuse pattern = diffuse large B cell lymphoma
Treatment strategies in lymphoma
Chemotherapy
Radiotherapy if localised/ bulky sites
Monoclonal antibody therapy - every mature B cell patient which is most (expresses CD20) e.g. Rituximab
Emerging new target therapy
Stem cell transplantation
Steroids/ anti-histamine/ paracetamol - prevent infusion reaction symptoms
Side effects of monoclonal antibodies
No/ mild symptoms
Mild reaction first infusion then tolerate subsequent
Few have severe infusion related reactions as immune system reacts to presence of foreign protein (cytokine release syndrome)
Heaviness in chest, hyperventilation, N&V, shivering uncontrollably, back pain, fever, BP drops (omit anti-hypertensive meds 12hrs prior), facial flushing
- gradually increase dose
3 examples of monoclonal antibodies used in treatment of solid cancer
Trastuzamab - inhibits HER-2 signalling
Bevacizumab - inhibits VEG-F signalling (stops BV growth near cancer)
Nivolumumab - inhibits CTLA-4 signalling (checkpoint T cell inhibitor so become activated)
Two examples of monoclonal antibody used in treatment of autoimmune conditions
Infliximab- inhibits TNF- alpha e.g. crohn’s, ulcerative colitis, RA, ankylosing spondylosis, psoriasis
Adalimumab inhibits TNF- alpha e.g. RA, psoriatic arthritis, Crohn’s, UC, psoriasis, AS
Example of monoclonal antibody used to treat cardiac problems
Abciximab - inhibits platelet glycoprotein 2b/ 3a
Prevents clots by thinning blood
One example of a MCAB used to treat an endocrine condition
Denosumab - inhibits RANK ligand on osteoclasts
For osteoporosis
