• Describe the current and future therapeutic strategies of autoimmune disease LO
1. Uses of monoclonal antibodies?
Diagnostics – in multiple laboratories
Therapeutic – 2 main categories of disease
• Blood / Haematological cancers
• Solid Tumours
- Auto-immune conditions
- Exciting targeted treatment
1. Monoclonal antibodies are ?
2. The generation of hybridomas involves?
1. monovalent antibodies which bind to the same epitope and are produced from a single B-lymphocyte clone
2. - inject epitope (part of an antigen)
- harvest B-lymphocytes from the spleen
- The B-lymphocytes + myeloma (myeloma) cell
- hybridoma cells -> cultured
- Selected hybridomas are found making a specific desired clonal antibody
What is an epitope?
part of an antigen molecule to which an antibody attaches itself
Monoclonal antibodies – examples of how they work (5)
Binding with cell surface receptors to:
1. activate or inhibit signalling within the cell
2. induce apoptosis
- antibody-dependent cell-mediated cytotoxicity (ADCC) or
- complement-dependent cytotoxicity (CDC)
4. Internalization (ie being taken in by the cell through the membrane) for antibodies delivering toxins into the cancer cell
5. Blocking inhibitory effects on T cells .. Thus activating T cells to help ‘kill’ the cancer cells
What does chimeric and humanised mean?
chimeric (murine variable regions and human constant regions)
humanized (human with murine complementarity-determining regions),
1. These B cells express ?
2. What can happen to the normal structure of the lymph node
1. CD 20
2. The lymph node can be taken over by small clonal B lymphocytes which retain the follicular pattern = Follicular lymphoma
OR by larger clonal B lymphocytes which take over the node in a diffuse = Diffuse large B cell lymphoma
A 21 yr old man presents with: swollen nodes in his arm pits and groin dry cough (worse lying flat) progressive breathlessness night sweats over past 4 weeks.
This turned out to be ?
The pathologist shows us that the lymphoma cells express CD 20.
Diffuse large B cell lymphoma, a high grade lymphoma.
A 75 yr old man presents with:
-discomfort in LUQ
- early satiety
- weight loss
- night sweats
gradual progression and worsening of symptoms over 9 months
This turned out to be ?
The pathologist shows us that the lymphoma cells express CD 20
Follicular lymphoma, a low grade lymphoma
What strategies are used to treat lymphoma?
• Monoclonal antibody therapy
• Emerging new targeted therapy
• Stem cell transplantation
• The 2 cases shown both received chemotherapy, steroids and Rituximab (a monoclonal antibody against CD20)
Where is CD20 located? Clinical significance?
- therapeutic target for B-cell malignancies
- CD 20 is expressed on the surface of all B cells
Why do we use anti-CD20 monoclonal antibody (R) to treat B-cell lymphoma?
Increase rate of survival
• The first big (399 patients) randomised trial of chemo v R-chemo in 60-80 year olds showed:
• Improvement in complete remission rate at end of treatment 63% to 75%
• 10 years later: improvement in people alive 28% to 44%
• Results highly significant
The symptoms and signs of IRRs (Infusion- related reactions) :
very few get IRRS from monoclonal antibodies
• Facial flushing
• Nausea and vomiting
Give examples of the uses of monoclonal antibodies and the drug given for the disease