Unit 2 - Antibody therapeutics Flashcards
What is antithymocyte globulin?
Purified gamma globulin (serum of rabbits immunised with human thymocytes)
How does antithymocyte globulin work?
Contains antibodies that binds to
- CD2
- CD3
- CD4
- CD8
- CD11a
- CD18
- CD25
- CD28
- CD44
- CD45
- HLA class I
- HLA class II
What effect do the antibodies in antithymocyte globulin have?
Antibodies deplete circulating lymphocytes by direct cytotoxicity
- complement (CMC)
- cell-mediated (ADCC)
Binding to cell surface molecules block lymphocyte function, leading to induction of apoptosis
What are the side effects of antithymocyte globulin?
Fever and chills with or without hypotension (major side effect)
Possibly premedicate with corticosteroids, H-blocker
Serum sickness and glomerulonephritis
Anaphylaxis
Leukopenia and thrombocytopenia
Risk of infection
Antibody development
- 68% of patients developed anti-rabbit antibodies
How are therapeutic proteins produced?
Polypeptides produced in microorganisms and cells
- humans
- animals
Give some examples of therapeutic proteins?
- hormones
- cytokines
- enzymes
- fusion proteins
- antibodies
What are the five classes of antibody?
IgG IgA IgM IgD IgE
What is the structure of IgG?
Monomer
What two essential functions do antibodies perform?
- antibodies bind to an epitope on an antigen with the arms of the Y. Each arm or monovalent antibody fragment (Fab 1) domain contains a binding site, making each antibody molecule at least bivalent
- the Fc domain of the Y imparts the antibody with biological effector functions such as natural killer cell activation, activation of the classical complement pathway and phagocytosis
What is a monoclonal antibody?
One type of antibody, complementary to one type of antigen, made by one type of plasma cell
What is a polyclonal antibody?
Antibodies from multiple B cells that bind to a single antigen with specificity for MULTIPLE epitopes on that antigen
What is a hybridoma?
A mouse B-lymphocyte cell and a tumour cells fused together so that as it divides many of the same antibodies are produced
What are the advantages of therapeutic antibodies?
- ability to bind with high specificity and affinity to a wide variety of molecules
- stable molecules, thus ideal molecules to be used as targeting reagents
What are the disadvantages of therapeutic antibodies?
- the first monoclonal antibodies were murine molecules and were recognised as foreign when infected into patients, leading to their elimination by the patient’s immune system
- in order to be effective, antibodies often need to interact with certain elements of the immune system such as receptors displayed on effector cells or the complement cascade. Murine antibodies could not do this
What is a chimeric antibody?
Fusion of murine variable domains, responsible for the binding activity, with human constant domains
- 70% human
- fully human Fc portion
- less immunogenic in humans
- interaction with human effector cells and the complement cascade