3.2.2 Types Of Monoclonal Antibdoies Flashcards
What is immunogenicity?
Ability of a foreign substance e.g. antigen, to provoke an immune response
What are the different types of monoclonal antibodies?
Murine 0% human, extremely high risk -omab suffix
Chimeric 65% human, high risk -ximab suffix
Humanised >90% human, low risk -zumab suffix
Fully Human 100% human, very low risk-umab suffix
What are conjugated monoclonal antibodies?
Antibody, linker and cyotoxic compound
Cytotoxic compound delivered directly to cell targeted by monoclonal antibody causing cell death
What are the benefits of conjugated monoclonal antibodies?
Persist in circulation
Can be internalised by cancer cells
How are conjugated MABs internalised?
Via receptor mediated endoycytosis
Lysosomes degrade the antibody and the cytotoxic contents are released
What are bispecific monoclonal antibodies?
Both arms of the Fab regions normally bind to the same thing
Bispecific monoclonal antibodies the two arms are able to bind to 2 different things, effector T cell and B cell
Used in B cell lymphomas
Antibody brings B and T cells together, T cell then stimulated and attacks B cell bound to other arm by releasing perforin
What receptors do MABs bind to on T and B cells in bispecific MABs?
B cell- CD20
T cell- CD3
How do MABs attack cancer?
- Binding with cell surface receptors to 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)
- Internalisation for antibodies delivering toxins into the cancer cell
- Blocking inhibitory effects on T cells, thus activating T cells to help kill cancer cells
How do checkpoint inhibitors work?
Inhibition present on T cells to stop immune system from damaging itself
Cancer usually increases inhibitory effects on T cells, meaning the cancer isn’t targeted by T cells
If this inhibiton is stopped then T cells can kill cancer cells
What is cluster of differentation classification?
Anitgens can be grouped together allowing cells to have an immunophenotype
Cancer cells have specific immunophenoytpes, thus they can be targeted
What type of cancer is lymphoma?
Hodgkins- B cells only
characterised by Reed-Sternberg cells
Non-
Hodgkins- B or T cell neoplasms
Lymphoma typically causes enlargement of lymph nodes
What other areas can be affected by lymphoma?
Extra-nodal areas:
Spleen
Bone marrow
Liver
Skin
Testes
Bowel
What do people with lymphoma often complain of?
Drenching night sweats
Fevers
Weight loss, more than 10% over 6 months
Dry cough- hilar lymph nodes affected
Early satiety- enlarged spleen compresses stomach
What are the two types of B cell lymphomas?
Follicular lymphoma
- Lymph node taken over by small clonal B lymphocytes which retain their follicular pattern
Diffuse large B cell lymphoma
- Lymph node taken overy by larger clonal B lymphocytes
- Take over the node in a diffuse pattern
What CD do follicular lymphoma and diffuse large b cell lymphoma have?
CD20
How is lymphoma staged?
Ann Arbor staging
What imaging is used to detect lymphoma?
Positron Emission Tomography- PET scan
Lymphomas are highly metabolically active so they show up very well on PET scans
How is lymphoma diagnosed?
Biopsy
How is treatment determined for lymphoma?
Immunohistochemistry on biopsy sample to detect the CDs present to check susceptibility
What treatment stratergies are used for lymphoma?
Chemotherapy- combined, non-overlapping toxicity
Raidotherapy- local parts of body, used early or for symptom control
Monoclonal antibody therapy
New targeted therapy
Stell cell transplantation- allogenic (someone else), autologous (self)
Give an example of a MAB against CD20
Rituximab
Why are MABs used in lymphoma?
Significantly improved complete response rates to chemotherapy
Significantly improved survival
What are the side effects of MABs?
- No symptoms or mild, e.g. fatigue
- Mild reaction to 1st infusion then tolerate treatments after
- Severe infusion related reactions as immune system reacts to foreign protein
What happens if you infuse MABs too quickly?
Hyperventilation
Nausea/vomiting
Shivering
Back pain
Heavy chest
What can be given to stop nausea due to MABs?
Metoclopramide and IV steroids
Antihistamines to stop facial flushing
What is involved in patient education with managing infusion related reactions?
Patient education
- Explain to the patient they may still have side effects after premedication
- Tell patient to inform staff of any change so staff can take immediate action
- Tell patient to stop anti-hypertensives for 12 hours prior to infusion
What pre-medications should be given to prevent reactions?
Steroids
Anti-histamines
Paracetamol
How should infusions be given to stop reactions?
Infusions started slowly, increased if they are tolerated
Drugs to stop reactions should be given prior to starting treatment
What MABs are given for solid cancer?
- Trastuzumab – inhibition of HER-2 signalling
- Ipilimumab – inhibition of CTLA-4 signalling
- Nivolumab/Pembrolizumab – inhibition of PD1 signalling (checkpoint inhibitors)
What MABS are given for autoimmune conditions?
Infliximab and Adalimumab – inhibition of TNF-alpha
What MABs are given in cardiology?
Abciximab – inhibition of platelet glycoprotein IIb/IIIa
What MABs are given for respiratory conditions?
Mepolizumab – inhibition of IL-5
What MABs are given in dermatology?
Ustekinumab – inhibition of IL-12 and IL-23
