Lecture 7 - Monoclonal Antibodies Flashcards
What is an antibody?
Immunoglobulin secreted by B cells (plasma cells)
What are the 2 main parts of an antibody?
Fab. (Fragemtn antibody region)
Fc (fragment crystallisable region)
What is the function of the variable fragment antigen region of the antibody?
Where antigens bind to the antibody
What is the paratope?
What is the epitope?
Epitope = antibody binding site on antigen
Paratope = antigen binding site on antibody
What is the fraction crystallised region of the antibody?
Part that binds to immmune cells
What are the uses of monoclonal antibodies/
Diagnostic tests (fluorescent tags)
Therapeutics (medicines)
What is a monoclonal antibody?
Mono alert antibodies which bind to the same epitope (on antigen) and are produced from a single B lymphocyte clone
How are monoclonal antibodies produced?
Hybridoma technique
What is the hybridoma technique of producing monoclonal antibodies?
Antigen injected into mouse, B lymphocytes producing antibodies to antigen are harvested
B lymphocytes then fused with immortal myeloma producing the hybridoma
What are the 3 types of monoclonal antibodies/
Naked monoclonal antibodies
Conjugated monoclonal antibodies
Bisepcific antibodies
What are the different types of naked monoclonal antibodies?
Murine (0% human)
Chimeric (65% human)
Humanised (>90% human)
Fully human
What is the suffix for murine naked monoclonal antibodies?
-omab
What is the suffix for chimeric naked monoclonal antibodies?
-ximab
What is the suffix for humanised naked monoclonal antibodies?
-zumab
What is the suffix for fully human naked monoclonal antibodies?
-umab
What are conjugated monoclonal antibodies?
Where antibodies are linked to a toxic compound so the toxin can be directly delivered to the target site
What are bispecific antibodies?
Where antibodies bind to 2 or more different epitopes at once
What is an example of use of bispecific antibodies?
Binding to tumour antigen and T cells to bring T cell closer to tumour cell so can engage it better
How do monoclonal antibodies generally work?
Bind to cell surface receptors either activating or inhibiting signalling
Bind to induce death
Surface receptor binding causing:
-antibody dependant cell mediated cytotoxicity
-complement (complement cascade) dependant cytotoxicity
Conjugate antibodies being internalised into cell (delivering toxin)
Activating T cells to destroy cancer cells
What generally happens in antibody-dependant cell mediated cytotoxicity?
Antibody binds to antigen leading to phagocytosis
What is lymphoma?
Blood cancer of mature lymphocytes (B cell or T cell type neoplasms)
What type of lymphocytes does lymphoma most commonly affects?
B cell
What parts of the body can be affected in lymphoma?
Enlarged lymph nodes
Spleen
Bone marrow
Liver
Skin
Testes
Bowel
What are the common symptoms of lymphoma called?
B symptoms
What are the B symptoms seen in lymphoma?
Drenching night sweats
Fever > 38
Weight loss
How do you diagnose lymphoma?
PET scan
CT
Biopsy (excision biopsy)
What is a lymphoma called when the B lymphocytes retain the follicular pattern?
Follicular lymphoma (most common low grade lymphoma)
What is the most common aggressive lymphoma which takes of the lymph node in a diffuse pattern?
Diffuse large B cell lymphoma
What receptors do B cells in lymphoma express?
CD20
Look at slide 19
What is the diagnosis
Slide 20
Diagnosis?
What are the treatment strategies in lymphoma?
Chemotherapy
Radiotherapy
Monoclonal antibody therapy
Emerging new targeted therapy
Stem cell transplant
How does Rituximab used to treat lymphoma?
Monoclonal antibody which targets CD20 on B cells
What type of antibody is rituximab?
Chimeric naked antibody
What is a standard treatment strategy for lymphoma?
Chemotherapy
+
Steroids
+
Rituximab
What is the mechanism of action of Rituximab? (what type of cytotoxicity does it stimulate?)
Binds to CD20 causing antibody dependant cell mediated cytotoxicity
What are the side effects of monoclonal antibodies like rituximab?
Usually very well tolerated
Mild fatigue
Mild reaction to first infusion (due to being chimeric antibody)
Very few have severe infusion related reaction
What drugs are given if patient starts having infusion related reaction?
Intense facial flushing, nausea and vomiting
Infusion stopped
IV steroid , if still not resolved give another IV steroid
Then IV metoclopramide for the nausea
What drug is given to patients that develop an infusion related reaction towards the end?
Anti histamine
How can we manage infusion related reactions?
Education (may still get side effects even with premedication, should inform staff if think gonna have reaction)
Premedicate ( steroid, antihistamine, paracetamol)
Slow infusion rate
What is tumour lysis syndrome?
Where rapid tumour break down leads to lots of uric acid being released leading to Hyperuricaemia
Hyperuricaemia can lead to formation of Urate crystals in the renal tubules leading to acute kidney injury which can lead to further metabolite disturbances
What are the 3 types of monoclonal antibodies for solid cancers?
Trastuzumab
Ipilimumab
Nivolumab
What is the mechanism of action trastuzumab in treating solid cancer?
Inhibitions of HER-2 signalling
Good in Herceptin receptor 2 positive breast cancer
What is the mechanism of action of nivolumab in treating solid cancer?
Inhibition of PD1 signalling
What are some monoclonal antibodies used to treat autoimmune conditions?
Infliximab
Adalimumab
How does infliximab and adalimumab work to treat autoimmune conditions?
Inhibts TNF-a
What is the main monoclonal antibody used in cardiology conditions?
Abciximab
What is the mechanism of action of abciximab?
Inhibits the platelet glycoprotein IIb/IIIa
What is the monoclonal antibody used to treat respiratory conditions?
Mepolizumab
What is the mechanism of action of mepolizumab?
Inhibts IL-5
What is. The mechanism of action ustekinumab?
Inhibits IL-12 and IL-23
