Session 3

Question 1

• Describe the current and future therapeutic strategies of autoimmune disease LO

1. Uses of monoclonal antibodies?

Answer 1

Diagnostics – in multiple laboratories

Therapeutic – 2 main categories of disease

• Cancer
• Blood / Haematological cancers
• Solid Tumours
• Auto-immune conditions
• Exciting targeted treatment

Question 2

Monoclonal antibody

1. Monoclonal antibodies are ?
2. The generation of hybridomas involves?

Answer 2

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

Question 3

What is an epitope?

Answer 3

part of an antigen molecule to which an antibody attaches itself

Question 4

Monoclonal antibodies – examples of how they work (5)

Answer 4

Binding with cell surface receptors to:

1. activate or inhibit signalling within the cell
2. induce apoptosis
3. Activate:
   - 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

Question 5

What does chimeric and humanised mean?

Answer 5

chimeric (murine variable regions and human constant regions)

humanized (human with murine complementarity-determining regions),

Question 6

1. These B cells express ?
2. What can happen to the normal structure of the lymph node

Answer 6

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

Question 7

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.

Answer 7

Diffuse large B cell lymphoma, a high grade lymphoma.

Question 8

A 75 yr old man presents with:

• back pain
• 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

Answer 8

Follicular lymphoma, a low grade lymphoma

Question 9

What strategies are used to treat lymphoma?

Answer 9

• Chemotherapy
• Radiotherapy
• 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)

Question 10

Where is CD20 located? Clinical significance?

Answer 10

• therapeutic target for B-cell malignancies
• CD 20 is expressed on the surface of all B cells

Question 11

Why do we use anti-CD20 monoclonal antibody (R) to treat B-cell lymphoma?

Answer 11

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

Question 12

The symptoms and signs of IRRs (Infusion- related reactions) :

Answer 12

very few get IRRS from monoclonal antibodies

• Hypotension
• Rigors/chills
• Facial flushing
• Dyspnoea
• Tachycardia
• Headache
• Fever
• Nausea and vomiting

Question 13

Give examples of the uses of monoclonal antibodies and the drug given for the disease

Answer 13