Monoclonal Antibodies - 6 Flashcards
what is a monoclonal antibody (MCA from here on)
a single unit that will bind to one antigen and recognise only one antigen
it can then bind to affector cells and trigger an immune response
key benefit - so can be used for very specific targeting
give uses and examples of MCA’s in clinical practice
diagnostics
- immunohistochemistry
immunofluroscopy
theraputics such as (only examples, dont know) adalimummab rituximab trastuzumab
naming / types of MCA’s
- ximab - 65% human rest mouse
- zumab - 90% human
- umab - fully human
the more human the drug, the less toxic w/ less side effects
will stay in body longer
what are conjugated MCA’s
adds a toxic bit to it
when binds to a cell ie cancer cell
toxic bit fucks it up, with out damaging rest of system
what are bispecific MCA’s
bind ie a B cell lymphoma (BAD) and T cell each with one arm
now t cell next to bad cell - fucks it up
How do monoclonal antibodies work
these are some examples
maybe know one well
read rest
Binding with cell surface receptors to either
activate or inhibit signalling within the cell
• Binding to induce cell death
• Binding with cell surface receptors to activate:
antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC)
• 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
what type of cancer is lymphoma
then there is an example of one
what is the key drug - MCA for treating lymphomas
what needs to be present
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
examples
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 pattern. Diffuse large B cell lymphoma
Both These B cells express CD20
so treat with MCA’s - give Chemo, Steroids and Rituximab - a MCA against CD20
outline some side effects of mca’s
• 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
so may have to spread infusion over long time in little bits due to tolerance
how do we manage infusion related reacitons
- 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. - need good bp
• 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
these are some uses of MCA’s - across many disciplines
try and remember the names of 2-3 and what they target
Wide use of monoclonal antibodies
• Solid cancer
• Trastuzumab – inhibition of HER-2 signalling
• Bevacizumab – inhibition of VEG-F signalling
• Nivolumumab – inhibition of CTLA-4 signalling
- Autoimmune
- Infliximab and Adalimumab – inhibition of TNF-alpha
- Cardiology
- Abciximab – inhibition of platelet glycoprotein IIb/IIIa
- Endocrine
- Denosumuab – inhibition of RANK ligand on osteoclasts
