Session 4 Flashcards
What are monoclonal antibodies?
• Monoclonal antibodies are monovalent
antibodies which bind to the same
epitope and are produced from a single
B-lymphocyte clone
How are monoclonal antibodies made?
The generation of hybridomas involves immunising a certain species against a specific epitope on an antigen and then harvesting the B-lymphocytes from the spleen of the mouse Monoclonal antibody • The B-lymphocytes are then fused with an immortal myeloma cell line not containing any other immunoglobulin-producing cells • The resulting hybridoma cells are then cultured in vitro so only the hybridomas (i.e. the fusion between the primary B-lymphocytes and myeloma cells) survive • Selected hybridomas are found making a specific desired clonal antibody
Benefits of monoclonal antibodies
• Specific • Can be targeted against
almost any cell-surface
receptor
Types of monoclonal antibodies
Naked monoclonal antibodies
Conjugated monoclonal antibodies
Bispecific monoclonal antibodies
Naked monoclonal antibodies
1
Conjugated monoclonal antibodies
2
Bispecific monoclonal antibodies
3
How do monoclonal antibodies work
• Binding with cell surface receptors to either
• antibody-dependent cell-mediated cytotoxicity (ADCC) or • complement-dependent cytotoxicity (CDC)
activate or inhibit signalling within the cell • Binding to induce cell death • Binding with cell surface receptors to activate:
• Internalization (ie being taken in by the cell
through the membrane) for antibodies delivering
toxins into the cancer cell • Blocking inhibitory effects on T cells (checkpoints).
Thus activating T cells to help ‘kill’ the cancer cells
Monoclonal antibodies in haematology
• Understanding what antigens are present on cancer cells and on normal tissue we could try to develop specific targeted treatments. • Cluster of differentiation (CD) classification.
What type of cancer is lymphoma
• Lymphoma divided into B and T cell
neoplasms – clonal proliferations of lymphoid cells
• It typically causes enlargement of lymph
nodes • The spleen, bone marrow and other areas of
the body such as liver, skin, testes and bowel
(‘extra-nodal’) may also be involved • People with lymphoma often complain of
drenching night sweats, fevers and weight
loss .. But some have none of these
symptoms
The lymph node can be taken over by small clonal B lymphocytes which retain the follicular pattern Follicular lymphoma
These B cells express CD20
..or by larger clonal B lymphocytes which take over the node in a diffuse pattern. Diffuse large B cell lymphoma
Treatment strategies in lymphoma
• Chemotherapy • Radiotherapy • Monoclonal antibody therapy • Emerging new targeted therapy • Stem cell transplantation
Why use mAbs in lymphoma
• Trials comparing chemo v R-
chemo
• Significantly improved complete
response rates (63 v 75%) • Significantly improved survival (at
10 years 28% v 44%) • Results highly significant
Side effects of monoclonal antibodies
• Some have no or mild symptoms eg mild fatigue • Many have a mild reaction to the 1st infusion and then
tolerate subsequent treatments well • A few people will have severe infusion related
reactions as their immune system reacts to the
presence of a ’foreign’ protein
How do patients feel when we use anti-CD20 monoclonal antibody (R) to treat B-cell lymphoma?
Q
Managing infusion related reactions
• Patient education:
• Explain to the patient that even though they have received
premedication, they may still experience some side effects. • Explain that they should inform staff the moment of any change, so that
staff can take immediate action • Instruct patient to omit their anti-hypertension medication for 12 hours
prior to their infusion.
• Prevention with Pre-medication: steroid, anti-histamine,
paracetamol • Start at a slow infusion rate, slowly increase if tolerated • Drugs required to treat IRRs should be prescribed prior to
starting patients treatment
