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Flashcards in Session 3 Deck (13):
1

• 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

- Cancer

• Blood / Haematological cancers

• Solid Tumours

- Auto-immune conditions

- Exciting targeted treatment

 

2

Monoclonal antibody

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

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3

What is an epitope? 

part of an antigen molecule to which an antibody attaches itself

4

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 

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

5

What does chimeric and humanised mean?

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chimeric (murine variable regions and human constant regions)

humanized (human with murine complementarity-determining regions),

 

6

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

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.

 

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Diffuse large B cell lymphoma, a high grade lymphoma.

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

 

Follicular lymphoma, a low grade lymphoma

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9

What strategies are used to treat lymphoma?

 

• 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)

10

Where is CD20 located? Clinical significance? 

- therapeutic target for B-cell malignancies

- CD 20 is expressed on the surface of all B cells

 

11

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

 

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12

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

very few get IRRS from monoclonal antibodies 

• Hypotension

• Rigors/chills

• Facial flushing

• Dyspnoea

• Tachycardia

• Headache

• Fever

• Nausea and vomiting

13

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

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