Monoclonal Antibodies

Question 1

Monoclonal antibody structure

Answer 1

Fab - hypervariable binds to antigens

Fc - fragment crystallisation fragment binds to immune effector cells to illicit an immune response

Question 2

Use of monoclonal antibodies

Answer 2

Determines blood group
Pregnancy test
Therapeutics

Question 3

Monoclonal antibodies

Answer 3

Monovalent antibodies which bind to the same epitope and are produced from a single B lymphocyte clone

Question 4

Hybrids as

Answer 4

1. Immunisation against a certain antigen epitope
2. Harvest B lymphocytes from the spleen
3. Fused with myeloma cell lone not containing any other immunoglobulin containing cell
4. Cultured in vitro
5. Selected

Question 5

Types of monoclonal antibody

Answer 5

Murine - 0% human - omab
Chimeric - 65% human - ximab
Humanised - 90%+ human - Zumbab
Fully human - 100% human - umab

Question 6

Conjugated monoclonal antibodies

Answer 6

Antibody linked with drug kills cancer cells by apoptosis or preventing signalling

Question 7

Bispecific monoclonal antibodies

Answer 7

1. Simultaneously binds to B cells and T cells via the cd20 arm and cd3 arm
2. T cells are activated and kill B cells
3. Immunological complex is created
4. Perforin forms a pore and granzymes allow the passage through the pore
5. Specific cellular reactions cause apoptosis

Question 8

Mechanisms of monoclonal antibodies (4)

Answer 8

1. Bind with cell surface receptors to activate or inhibit signalling
   - antibody dependent cell mediated cytotoxicity (ADCC)
   - complement dependent cytotoxicity (CDC)
2. Induce apoptosis
3. Internalisation and delivery of toxins into cancer cell
4. Block T cell inhibition therefore T cells are activated to kill cancer cells

Question 9

Lymphoma

Answer 9

B and T cell neoplasms

Causes enlarged lymph nodes and may involve extra nodal lymph organs e.g. spleen

Question 10

Symptoms of lymphoma

Answer 10

Drenching night sweats
Fever
Weight loss

Question 11

Follicular lymphoma

Answer 11

Lymph node taken over by small colonial B lymphocytes which retain follicular pattern

Express CD20

Question 12

Diffuse large B cell lymphoma

Answer 12

Lymph node taken over by larger clonal B lymphocytes diffusely

Question 13

Treatment of lymphoma

Answer 13

Chemotherapy
Radiotherapy
Monoclonal antibody therapy e.g rituximab
Stem cell transplant

Question 14

Side effects of monoclonal antibodies

Answer 14

None/mild
Mild in first infusion then tolerate subsequent infusions 
Some may have severe side effects
- nausea and vomiting 
- shivering 
- chest infection 
- back pain

Question 15

Managing infusion related reactions

Answer 15

Patient education:

• May still have side effects
• should inform staff of any change
• omit hypertension medication 12 hours before infusion

Prevention with pre medication

• antihistamine
• paracetamol
• steroid

Start at slow infusion rate and slowly increase tolerance

Question 16

Wide use of monoclonal antibodies

Answer 16

Solid cancer:

• inhibit HER 2 signalling in breast cancer
• inhibit VEG-F signalling preventing angiogenesis

Autoimmune
- inhibition of TNF alpha

Cardiology
- inhibition of glycoprotein IIb/IIIa

Endocrine
- inhibition of RANK king and on osteoclasts