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Y3 immunology and haematology > immunotherapy > Flashcards

immunotherapy Flashcards

1
Q

what are the different immunosuppressive strategies

A

general immunosuppresive strategies

allergy and AI disease

blanket immunosuppression

opportunistic infection

strong need to develop tailored therapies that target the specific immune response but leave the rest of the immune system free to fight disease

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2
Q

immunosuppression for allergy

A

anti-histamine to prevent allergic response

corticosteroids for severe allergy

anti-IgE, leukotriene antagonists to prevent bronchial constriction in asthma

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3
Q

what is a risk with blanket immunosuppression

A

opportunistic infections

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4
Q

why is cyclosporin so important in transplantation

A

major step forward in transplant survival

esp for cardiac transplant

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5
Q

why is T cell suppression important in transplants

A

by suppressing the T cell response you can prevent acute rejection

e.g. cyclosporin, rapamycin

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6
Q

how does cyclosporin work

A

calcineurin inhibitor

prevents IL-2 production by the T cell

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7
Q

how does rapamycin work

A

targets mTOR (mechanistic target)

targets IL-2 uptake by the T cell

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8
Q

what are the different types of immunty

A
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9
Q

how does natural active immunity work

A

person is infected with microbe

days-wks later will make a response - potent adaptive immune response

T cells and antibodies against the pathogen

develop ‘memory’ for that specific pathogen

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10
Q

how does passive immunity work

A

receive the antibody for a microbe from another individual

doesn’t result in memory against the pathogen as there has been no active immune response

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11
Q

examples of passive immunity

A

snake/spider bites, scorpion/fish stings - passive infusion of antibody specific for the toxin

hypogammaglobulinaemia - 1y or 2y infusion of gamma globulins to reduce infection

rabies immunoglobulin - post-exposure prophylaxis together w/ vaccination

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12
Q

immunoglobulin for post-exposure prophylaxis and what diseases are they given for

A

human normal immunoglobulin (HNIG):

  • hep A
  • measles
  • polio
  • rubella

specific immunoglobulins:

  • hep B
  • rabies
  • tetanus
  • VZV
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13
Q

what conditions is intravenous immunoglobulin used for

A

biologic therapy for 1y and 2y immune deficiencies and some AI disorders

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14
Q

what is IVIg

A

plasma derived IgG used for replacement therapy for

polyclonal IgG preparation usually given IV but can also be given SC

very high dose - 1-3g/kg

pooled from several thousand donors

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15
Q

what is direct (targeted) immunotherapy

A

antibodies or antibody related fragments that detect an antigen on the tumour cell and destroy the target either by recruiting immune cells or by delivering a toxin or radioisotope to it

targets tumours

recruit pro-inflammatory cells to kill tumour cells

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16
Q

what is indirect immunotherapy

A

immune system is activated rendering it able to seek and destroy tumour cells

targets immune system

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17
Q

what are ADCs

A

antibody drug conjugates

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18
Q

examples of direct immunotherapy

A

monoclonal antibodies

chimeric antigen receptors (CARs)

Bi-specific antibodies

-

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19
Q

what do bi-specific antibodies do

A

recognise a targeted antigen on a tumour cell

also have another target on immune cells for example - boosts immune cell activity set by specific antibodies

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20
Q

examples of indirect immunotherapy

A

tumour vaccines

dendritic cell vaccines

adoptive cell transfer

cytokine therapies

checkpoint inhibitor therapies

stimulatory antibodies

21
Q

what are dendritic cell vaccines

A

highly potent immune cells

can stimulate immune responses very effectively

combine tumour antigens w/ dendritic cells to drive T cell responses

22
Q

what is adoptive cell transfer

A

cell transfer therapies where the cells have been trained to generate immune responses against the tumour antigens

23
Q

what are cytokine therapies and what are they used for

A

immunomodulatory cytokines to activate anti-tumour immunity

pegylated IFN-alpha, IL-2, GM-CSF (last one is for cancer recovery to boost neutrophil levels)
- pegylated = much longer serum half life

used in specific cancers

pegylated is an effective anti-viral IFN-alpha therapy and used in melanoma

24
Q

what is a polyclonal response

A

immunisation w/ antigen will typically lead to a polyclonal response

many different B cell clones will generate antibodies specific for the antigen

a number of epitopes will be bound by antibody

antibodies w/ different variable regions bind multiple epitopes

not that useful in clinical practice

25
Q

how are monoclonal antibodies produced

A

immunisation

fusion and immortalisation of B cells

isolation and screening

expansion of desired hybridoma

26
Q

what are car T cells

A

combination of antibody and T ell

used with multiple myeloma as a treatment

27
Q

types of antibodies used in therapeutic monoclonal antibodies

A 
human 
humanised - GE antibodies
chimeric - mix of mouse and human 
fragment - part antibody, part extracellular receptor 
murine - mouse
28
Q

what cancer is rituxan (rituximab) a first line treatment for

A

non-Hodgkins lymphoma

29
Q

how does rituximab work

A

specific for CD20 molecule on the cell surface of a small sub-population of B cells

wipes out most of B cell population by recruiting macrophages and NK cells

doesn’t cause opportunistic infection

30
Q

what other diseases can rituximab be used to treat

A

highly beneficial in RA and SLE

31
Q

what type of therapy is infliximab

A

anti-TNF

32
Q

what is infliximab used to treat

A

RA
ankylosing spondylitis
crohn’s disease
ulcerative colitis

33
Q

how does infliximab work

A

chimeric antibody that blocks the function of tumour necrosis factor alpha

34
Q

what is TNF and what does it stimulate

A

pro-inflammatory cytokine

stimulates an acute phase reaction

35
Q

what is herceptin - trastuzumab - used for

A

treatment of HER2 +ve metastatic breast cancer (human epidermal growth factor receptor 2)

previously sufferers had a very poor prognosis

36
Q

how does herceptin - trastuzumab work

A

antibody binds HER2 on cancer cells and marks them out for destruction by the immune system

37
Q

what % of breast cancers are HER2+ve

A

15-20%

38
Q

example of new anti-HER2 antibodies and how they work

A

pertuzumab

directed at the dimerisation domain of HER2 - disruption of dimer formation

disrupts signalling complex and signalling to the cell and prevents the cancer cell from growing uncontrollably

39
Q

what is Skyrizi - risankizumab - used to treat

A

plaque psoriasis

trials in crohn’s and psoriatic arthritis are ongoing

40
Q

what is the target for risankizumab and what type of antibody is it

A

IL-23 p19 subunit

IgG1 humanised

41
Q

how does risankizumab work

A

selectively blocks IL-23 by binding to the p19 subunit

IL-23 - cytokine involved in inflammatory processes and thought to be linked to a number of chronic immune mediated diseases

42
Q

what are checkpoint inhibitor antibodies and what do they do

A

unlock the gateway to the adaptive immune system

powerful anti-tumour responses

potential for immune related adverse effects

43
Q

example of anti-CTLA 4 antibody

A

ipilimumab

44
Q

how do checkpoint inhibitor antibodies work

e.g. anti CTLA-4 antibodies

A

dendritic cell (green) provides into to T cells about tumour antigens

MHC = tissue type molecule, presents yellow peptide antigen (from tumour cell)

TCR recognises the peptide and activates the T cell

B27 receptor on APC and CD28 on T cell ligate, T cell is fully activated and proliferates - destroys cancer

CTLA-4 is very similar to CD28 and also binds B27 and delivers inhibitory signal to shut T cell down - CTLA-4 antibodies block the inhibitory signal

45
Q

what is required for full activation of a T cell

A

ligation of the 2 receptors

46
Q

what is ipilimumab used for

A

metastatic malignant melanoma

47
Q

mode of treatment with dendritic cell vaccines

A

blood sample from patient

culture dendritic cells in vitro w/ cytokines that promote APC function

transfuse pts w/ APC after uptake of tumour antigen

induces T cell responses to kill cancer

48
Q

adoptive cell transfer - tumour infiltrating T cells

how is it done

A

excise tumour from pt

plate out fragments of tumour cells and purify tumour cells and T cells from the tumour

culture w/ IL-2

check they have specific tumour recognition then reinfuse back into the patient to kill the tumour cells

49
Q

what is CAR T cell therapy

A

CAR T cells are engineered to express antigen-targeted receptors specific for tumour antigens

CAR includes an antigen binding domain fused to a transmembrane domain followed by T cell activation domains associated w/ TCR

T cell modified w/ CAR now has new antigen specificity and binding its antigen supports T cell activation and killing of the target cell

Y3 immunology and haematology (20 decks)

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