immunotherapy Flashcards
general principles
controlling immune system
using immune system to fight disease
(immunosuppresion, immunomodulation)
general immunosuppresive strategies
corticosteroids
anti IgE
leukotriene antagonists
corticosteroids
affect T and B cell function
affects on cytokine networks, inflammation, T cell and monocyte function
azathioprine
purine analogue which inhibits DNA synthesis
inhibits T and NK cell function
antiinflammatory
cyclophosphamide
alkylating agent which interferes with DNA syntehsis
useful for suppressive B cell activity and antibody production (esp autoantibodies)
cyclosporin
pro-drug, require binding to cytoplasmic receptors to activate
modulation and down-regulation various genes e.g. transcription IL-2
immune suppression of T cells and NK cells
rapamycin
decrease IL-2 production by Th cells
mycophenolic acid
transplant rejection, Crohn’s
inhibitor of purine synthesis, prevents T cell proliferation
cytokine therapy
inhibit activity of harmful cytokines or enhance the activity of beneficial cytokines
immunoglobulin for post-exposure prophylaxis
human normal Ig: hepatitis A, measles, polio, rubella
specific Igs
- hep B
- rabies
- tetanus
- varicella zozster
IVIg
plasma derived IgG
key biologic for replacement therapy in 1ry and 2ry immunodeficiencies
also for some autoimmune disorders
what is IVIg
polyclonal IgG preparation usually given IV but can also be SCIg
very high dose - 1-3g/kg
IVIg indications
1ry immunodeficiency wiskott alrdick syndrome IgG subclass deficiencies with recurrent infections idiopathic thrombocytopenic purpura kawasaki disease
direct (targeted) immunotherapy
antibody related fragments that detect an antigen on tumour cell + destroy it by recruiting immune cells or delivering toxin/radioisotope to it
target = tumour
indirect immunotherapy
immune system is activated rendering it able to seek and destroy tumour cells
boost immune response to kill cancer
target = immune system
direct immunotherapy examples
monoclonal antibodies
chimeric antigen receptors (CARs)
bi-specific antibodies
indirect immunotherapy examples
tumour vaccines dendritic cell vaccines adoptive cell transfer cytokine therapies checkpoint inhibitor therapies stimulatory antibodies
cytokine therapy
immunomodulatory cytokines to activate anti-tumour immunity
pegylated IFN-alpha, IL-2
polyclonal response
immunisation with antigen will typically lead to a polyclonal response
many different B cell clones will generate antibodies specific for antigen
a number of epitopes will be bound by antibody
antibodies with different variable regions bind multiple epitopes
monoclonal antibodies
isolate single antibody producing clone and grow it in vast quantities
specific sensitivity, recognises one epitope
rituximab
1st line for NH lymphoma
specific for the CD20 molecule of cell surface of small sub-population B cells
benefits in RA and SLE too
how does rituximab work
targets leukaemic/lymphoma B cell
recruits immune system to kill it: macrophages, NK cells, complement system
infliximb: anti-TNF
RA, ank spond, Crohn’s UC
chimeric antibody that blocks function of TNF-alpha
herceptin
antibody binds to HER2 on cancer cells and marks them for destruction by immune system
HER2 +ive breast cancer
the checkpoint inhibitors
powerful anti-tumour responses
CAR T cell therapy
CAR T cells are engineered to express antigen-targeted receptors for specific tumour antigens
T cell modifies with CAR has new antigen specificity
activation and killing target cell
