Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BMS 379 Cancer biology > Lecture 12- Cancer immunotherapy > Flashcards

Lecture 12- Cancer immunotherapy Flashcards

You may prefer our related Brainscape-certified flashcards:
AP® Biology flashcards Biology 101 flashcards
1
Q

Mechanism by which tumours evade the immune system - see diagram

A
  • Low immunogenicity
  • Tumour treated as self antigen
  • Antigenic modulation
  • Tumour induce immune suppression – secret factors to suppress immune cells
  • Tumour induced privileged site – secrete factors to form a physical barrier
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Innate immunity

A

Short term

defence is inborn or innate in that its action does not depend on prior exposure to a particular pathogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Adaptive immunity

A

Long term -

- immunity is acquired during the lifetime of the individual as an adaptive response to a particular pathogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Innate immunity - cell s

A
  • Neutrophils
  • Macrophages
  • NKCs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Adaptive – cells

A
  • -APC
  • Lymphocytes
    B or T cells
    Anti tumour ability – ability to attack the c=tumour cells
  • Response to cytokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Hallmarks of Cancer

A 
Growth self-sufficiency
•  Evade apoptosis
•  Ignore anti-proliferative signals 
•  Limitless replication potential 
•  Sustained angiogenesis
•  Invade tissues
•  Escape immune surveillance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What dictates the type of response ?

A

Cell type

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Recognition mechanisms of innate immunity

A

Rapid response
Invariant
limited number of specificities
constant during response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Recognition mechanisms of adaptive/acquired immunity

A

slow response
variable
numerous highly selective specificities
improve during response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Steady State

A
  • Embryonic progenitor derived macrophage
  • Monocyte derived Macrophage
    >Tissue homeostasis
    > Tissue specific functions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Infection

A

-Effector Monocyte/macrophage/DCC
>Recruitment
- Tissue resident macrophage
> Expansion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Tumour

A

trTAM
tiTAM
- immune modulation
- dysregulated maintenance of tissue homeostasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Tumour associated Macrophages

A

M2 and M1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

TAM- M1

A 
Scarce 
Immunostimulatory 
Pro-inflammatory 
Tumoricidal 
Perform ADCC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

TAM- M2

A 
Pro -tumour 
Predominant 
Immunosupressive 
Pro-angiogenic 
Maintain T-regs 
Do not perform ADCC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Majority of tumours contain

A

macrophages

17
Q

Immunotherapy

A

– harness immune system to kill tumours

Induce immune response against tumours

18
Q

Timeline

A

1850 – patients with cancer tumours – tumour would shrink in response to another infection

1985- T cells taken from patient expanded and put them back in
1990 – discovery of checkpoint inhibitors
2015- oncolytic HSV virus used to treat melanoma

19
Q

5 types of immunotherapy

A
  1. Monoclonal antibodies
  2. Immune check point inhibitors
  3. Cancer vaccines
  4. Adoptive cell transfer
  5. Cytokines
20
Q

Immunotherapy-Active

A

vaccination, augmentation of host immunity to tumours

21
Q

Immunotherapy - Passive

A
  1. Adoptive Cellular Therapy (T cells) 2. Anti-tumour Antibodies (Her-2/Neu,
    CD20, CD10, CEA, CA-125, GD3 ganglioside)
22
Q

Cell based therapy

A

Can be used to active a patients own immune system to attack cancer
Can be used for delivery of therapeutic agent
Dendritc cells popular choice of cell

23
Q

Dendritic cell-

See diagram

A
  • Found throughout the body (0.1-0.5%)
  • Interstitial cells (Liver, heart, liver), Langerhans cells of the epidermis.
  • Detect and chew up foreign “invader” proteins and then “present” piece of the invaders on their surface.
  • To make a DC vaccine, the blood of the cancer patient is collected and enriched to increase the population of DC.
24
Q

Active Immunotherapy - Vaccines

A
  1. Killed tumour vaccine
  2. Purified tumour antigens
  3. Professional APC-based vaccines
  4. Cytokine- and costimulator-enhanced vaccines 5. DNA vaccines
  5. Viral vectors
25
Q

T cells- Killer Cells

A

Tumour biopsy

  1. Tumour Fragments (Isolation) and TIL separated
  2. TILs propagated on tumour fragments - (Cultivation)
  3. Melanom Reactive TILS (Expansion)
  4. T cell fusion
26
Q

Trojan Horse- Treatment

A

City of troy – tumour need to access
Horse – macrophages
Macrophages go in – produce a virus which replicate and infect more cells and attach the tumour
-
TAMs accumulate in hypoxic areas
Extract blood > monocytes > macrophage > therapeutic macrophage (with virus) > tumour
Hypoxic tumour cells grow

27
Q

Hypoxia

A

Hypoxia (low oxygen) is a prominent feature of malignant tumours Inability of the blood supply to keep up with growing tumour cells Hypoxic tumour cells adapt to low oxygen- increase there survival

28
Q

Tumour hypoxia

A

Poor patient prognosis

  1. Stimulates new vessel growth
  2. Suppresses immune system
  3. Resistant to radio- and chemotherapy (repopulate the tumour)
  4. Increased tumour hypoxia after therapy
29
Q

macrophages in tumours

A

can get deep into tumours

- in most cells

30
Q

macrophages

A

Great receptors

  • big eaters
  • add anything they take it up
31
Q

Evidence of hypoxia increase with therapy use

A

prostate cancer mice models

  • treat with Doxacetl
  • increase in hypoxia
  • leads to more macrophages been taken to the tumour
32
Q

Combo approach- use classic therapy followed by macrophage therapy

A

used-
Naked mice with no adaptive immune system- grow human cells inside the mice
- implant tumour
- inject macrophage therapy
- 48 hours later removed tumour to see if therapy has reached it
- within the hypoxic area of the 3 million macrophage added only small number get there but widespread production of the virus
- only need a small number to spread a lot of virus

33
Q

Trojan horse therapy combined with Docetaxel

A

When you give docetaxel and macrophage therapy you can shrink and keep tumours small
- stops metastasis from developing

34
Q

Trial

A
  • Funded then dropped
  • virus made for a study injecting directly into prostate
  • Idea could get to all tumours in the body
  • 1.4 million to make the virus
  • enough for the trial nut not enough to be stability tested
35
Q

Magnetic macrophage therapy –

A
  • MRI to steer magnetic macrophages to deep tumour lesion s
  • Monocytes removed from patients insert therapeutic virus load with MNPs
  • Macrophages circulate in bloodstream- steered to target by magnets
36
Q

in vivo targeting of magnetic macrophages in mouse models -

A

Day 0 - inject prostate tumour cells
Day 28-
prepare macrophages and transfect with pmaxgfp
Day29-
load macrophages with MNP and administer to mice by tail vein injection
-Anaesthetise mice and apply magnetic field to surface of tumour for 5 hr
-Kill mice divide tissue into two, snap freeze half and run remainder through FACs

37
Q

Magnetic macrophages traffic to the prostate tumours

A

5 % of macrophages getting to tumour with no magnet
15% of macrophages getting to tumour with magnet
- improving drug delivery -less drug needed> less toxicity

38
Q

Issue with the current research with magnetic macrophages

A
  • currently tested on surface tumour which can be surgically removed anyway
39
Q

MRI

A

target deep into the tumour
- locate tumour with MRI
- program Magnetic field to the tumour - pulsed on and off
Removed tumours – and looked to see had more therapy got to more of the tumour – 4% to 7% nearly half had got to tumour - improved the therapy
- image the tumour before and after > dark patches at the end

BMS 379 Cancer biology (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions