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cellular basis of immunity > 14 - cancer immunotherapy > Flashcards

14 - cancer immunotherapy Flashcards

(49 cards)

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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

Study These Flashcards
A

passive
- therapeutic monoclonal antibodies

active
- e.g. HPV vaccine

21
Q

other methods of immunotherpay (3)

Study These Flashcards
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

Study These Flashcards
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

Study These Flashcards
A

radioimmuno conjugates
immunocytokine
immunotoxin
immunoliposome

24
Q

radioimmunoconjugate

Study These Flashcards
A

antibody bound to radionuclide which provides energy to kill cancer cell

25
limitations of immunotoxins
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
Bettsy Patterson
diagnosed with Non Hodgkins Lymphoma cancer lots of chemotherapy treatment lots of horrible side effects and no permanent effective cancer treatment --> NHL returns
27
first monoclonal antibody treatment approved for | cancer
Rituximab
28
Rituximab
chimeric human-mouse mAb targeted against CD20 on B cells | lyses CD20 via ADCC or human complement pathway
29
effect Of Rituximab on Bettsy
tumour decreases nodes disappear pain decreases very few side effects
30
mutations in BCRA2 tumour suppressor gene
increased chance of breast or ovarian cancer
31
HER2
unique antigen expressed on surface of breast cancer cells
32
herceptin
humanised monoclonal antibody blocks attachment of human epidermal growth factor to HER2 prevents growth and division of breast cancer cells
33
Sola
humanised monoclonal antibody (neuroprotector) binds to amyloid B peptides prevents build up of plaques in neurons causing alzheimers
34
Tocilizumab
humanised monoclonal antibody treatment of rheumatoid arthritis blocks binding of IL-6 no binding = no inflammation at joints
35
immune checkpoint modulation
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
mechanism of immune checkpoint protein inhibition
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
anti-CTLA4
antibodies can be used to prevent CLA4 binding to B7 | therefore increases T cell activation and cancer cell killing
38
Theralizumab - TGN1412
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
use of TILs in cancer therapy
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
method of TIL treatment
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
limitations of TIL treatment
expensive | time consuming
42
advantages of TIL treatment
can last for years
43
transgenic TILs
T cells are engineered to have a specific transgenic TCR which we know has high affinity to a certain tumour antigen
44
CAR-T cells
Chimeric Antigen Receptor Modified T Cells a form of adoptive immune cell therapy
45
method of CAR-T cells
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
importance of CAR
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
antibody-guided (molecular) imaging
``` radio-labelled antibodies used to located cancer cells by molecular imaging e.g. CT scans MRI PET ```
48
how does antibody-guided molecular imaging work
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
2 most promising immunotherapy tools
immune checkpoint inhibitors and CAR-T T cells

cellular basis of immunity (21 decks)

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