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cellular basis of immunity > 14 - cancer immunotherapy > Flashcards

14 - cancer immunotherapy Flashcards

1
Q

effect of immunocompromised on cancer

A

increases your susceptibilty

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2
Q

role of Il-2 and cancer

A

immunoprotective against cancer

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3
Q

TIL

A

tumour infiltrating T-lymphocytes

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4
Q

increased numbers of Tumour Infiltrating T-lymphocytes

A

linked to increased chance of cancer survival

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5
Q

hyperploidy

A

too many chromosomes

often seen in cancer cells

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6
Q

calreticulin

A

CRP55 protein

binds to unfolded proteins from abnormal nucleus to prevent them from being replicated

activates MHC I complex
causes macrophages to be activated to engulf cancerous cells
naive T cells become effector T cells

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7
Q

3 stages of cancer immune surveillance

A

1 - elimination
2 - equilibrium
3 - escape

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8
Q

cancer immune surveillance

equilibrium

A 
cancer cell recognition
CD8 T cell expansion
B cell activation 
NK cells and antibodies kill cells
T reg cells monitor immune response
death of some tumour cells
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9
Q

importance of equilibrium stage

A

cancerous tumour is contained by immune system but not completely destroyed

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10
Q

cancer tumour escape stage

A

tumour antigen editing via genomic instability
immune evasion
tumour no longer recognised by immune system
tumour microenvironment becomes immune suppressive

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11
Q

stage targeted by cancer immunotherpayh

A

tumour escape stage

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12
Q

impediments to anti-tumour therapy

A
  1. most tumour antigens are recognised as self antigens not as foreign
  2. chemotherapy is aggressive and destroys many healthy cells, depletes immune system
  3. tumour microenvironment suppresses immune system
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13
Q

immune suppressive signals of tumour microenvironment

A

increased no. of suppressive cytokines
decreased MHC I expression in tumour cells
infiltration of T reg cells –> inhibition of dendritic cells

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14
Q

co-stimulatory pairs important for

A

T cell activation

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15
Q

why do we need immunotherapy

A

radiotherapy and chemotherapy are potentially dangerous

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16
Q

advantages of cancer immunotherapy

A

more targeted and specific to cancer cells
more powerful (attacks cancer systemically)
universal (applies to all cancers)
has good memory (via T cells) –> durability of protection

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17
Q

increase in research into immunotherapy

A

after introduction of hybridoma technology and monoclonal antibody production

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18
Q

aim of immunotherapy

A

maximise immune activity and minimise immune suppressors

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19
Q

role of cancer vaccines

A

prime body against likelihood of having cancer

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20
Q

types of cancer vaccination

A

passive
- therapeutic monoclonal antibodies

active
- e.g. HPV vaccine

21
Q

other methods of immunotherpay (3)

A

immune system modulators
e.g. IL-2 activates CD8 T cells

immune checkpoint modulation
(changes the way T cells interact with co-stimulatory pairs)

immune cell therapy

22
Q

method of therapeutic monoclonal antibodies

A

carry cytotoxic agents to tumour
guides immune cells towards tumour
induce complement mediated lysis of tumour or ADCC
blocks activity of tumour-specific proteins with receptors
ultimately prevents division

23
Q

types of therapeutic monoclonal antibodies

A

radioimmuno conjugates
immunocytokine
immunotoxin
immunoliposome

24
Q

radioimmunoconjugate

A

antibody bound to radionuclide which provides energy to kill cancer cell

25
Q

limitations of immunotoxins

A

antibody must have high affinity and specificity for toxin or cause cause damage as highly toxic
have to be targeted to cancer cell then effective

26
Q

Bettsy Patterson

A

diagnosed with Non Hodgkins Lymphoma cancer
lots of chemotherapy treatment
lots of horrible side effects and no permanent effective cancer treatment –> NHL returns

27
Q

first monoclonal antibody treatment approved for

cancer

A

Rituximab

28
Q

Rituximab

A

chimeric human-mouse mAb targeted against CD20 on B cells

lyses CD20 via ADCC or human complement pathway

29
Q

effect Of Rituximab on Bettsy

A

tumour decreases
nodes disappear
pain decreases
very few side effects

30
Q

mutations in BCRA2 tumour suppressor gene

A

increased chance of breast or ovarian cancer

31
Q

HER2

A

unique antigen expressed on surface of breast cancer cells

32
Q

herceptin

A

humanised monoclonal antibody
blocks attachment of human epidermal growth factor to HER2
prevents growth and division of breast cancer cells

33
Q

Sola

A

humanised monoclonal antibody (neuroprotector)
binds to amyloid B peptides
prevents build up of plaques in neurons causing alzheimers

34
Q

Tocilizumab

A

humanised monoclonal antibody
treatment of rheumatoid arthritis
blocks binding of IL-6
no binding = no inflammation at joints

35
Q

immune checkpoint modulation

A

prevent over-stimulation that could be damaging
strength of interaction determines how upregulated the T cell will be
use antibodies and agonists/antagonists
cancer therapy targets immune checkpoint inhibitors

36
Q

mechanism of immune checkpoint protein inhibition

A
  1. co-stimulation via CD28 ligation –> transduction of T cell activation signals
  2. blockage of immune checkpoint protein (e.g. CTLA4) enhances T cell signalling
    - “brakes” on immune system released
37
Q

anti-CTLA4

A

antibodies can be used to prevent CLA4 binding to B7

therefore increases T cell activation and cancer cell killing

38
Q

Theralizumab - TGN1412

A

investigational immunomodulatory drug for rheumatoid arthritis
binds to CD28 co-stim pair on T cells

potent agonist
stimulates anti-inflammatory cytokine production e.g. IL-10

clinical trials in humans

  • dose too high
  • cytokine storm caused
39
Q

use of TILs in cancer therapy

A

able to target cancer cells
not enough within tumour to eradicate it or overcome immunosuppressive signals
attempts to introduce massive populations of activated TILs as treatment

40
Q

method of TIL treatment

A

TILs are collected from samples of the tumor

TILs that show best recognition of the patient’s tumour in lab are selected

Cells are activated with cytokines and re-infused into the patient’s bloodstream

41
Q

limitations of TIL treatment

A

expensive

time consuming

42
Q

advantages of TIL treatment

A

can last for years

43
Q

transgenic TILs

A

T cells are engineered to have a specific transgenic TCR which we know has high affinity to a certain tumour antigen

44
Q

CAR-T cells

A

Chimeric Antigen Receptor Modified T Cells

a form of adoptive immune cell therapy

45
Q

method of CAR-T cells

A

T cells collected from patient
T cells modified to express protein (chimeric antigen receptor)
Replace T cell receptor with antibody complex
Grow large populations in lab
CAR-T cells re-infused into patient

46
Q

importance of CAR

A

modified form of the T cell receptor
binds to cancer cells
once bound, T cell becomes activated and kills cancer cell

does not rely on MHC

47
Q

antibody-guided (molecular) imaging

A 
radio-labelled antibodies used to located cancer cells by molecular imaging
e.g. 
CT scans
MRI
PET
48
Q

how does antibody-guided molecular imaging work

A

antibody carries radioligand to cancer cell
radio ligand bound decays when bound to cancer cell
decay releases neutrons and positrons
positrons bind to electrons and release photons
picked up by PET or CT imaging

49
Q

2 most promising immunotherapy tools

A

immune checkpoint inhibitors and CAR-T T cells

cellular basis of immunity (21 decks)

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