Brainscape's Knowledge GenomeTM

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


See full index

MIIM30003 - Medical & Applied Immunology > Lecture 8 - Tumour Immunity 2 > Flashcards

Lecture 8 - Tumour Immunity 2 Flashcards

You may prefer our related Brainscape-certified flashcards:
USMLE® Step 1 flashcards
1
Q

Describe William Coley experiments with anti-tumour immunotherapy

A

1893

Coley observed a patient recover from cancer after a severe bacterial infection

He then isolated bacterial Ags: ‘Coley’s toxins’

When injected, Coley’s toxins induced tumour rejection

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

What is the key to the future of cancer therapy?

A

Immunotherapy

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

List some of the various approaches to cancer immunotherapy

A
  • Preventative therapies
  • Antibody therapy
  • Cytokine therapy
  • Immunisation w/ tumour Ags
  • Adoptive cell transfer therapy
  • Removal of immunosuppression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Discuss preventative immunotherapy against cancer

A

Immunise against viruses that can cause cancer

Examples:
• EBV
• HPV - Gardasil
• HBV

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

Which cancers do the following cause:
• EBV
• HPV
• HBV

A

EBV: Lymphoma, Non-Hodgkins Lymphoma

HPV: cervical cancer

HBV: hepatocellular carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe Ab therapy for cancer

A 
Approach:
 • mAb generated against tumour Ags
 • mAbs injected and act through a variety of mechanisms:
- Ligand blockade
- Receptor blockade
- Cell depletion
- Ab-conjugates
- ADCC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the use of conjugated mAb as cancer immunotherapy

A

Certain molecules are conjugated to mAbs. Conjugates are internalised, killing the tumour cell

  1. Radioisotopes
    • Delivers radiotherapy directly to tumour
    • Diminishes radiation to healthy cells
  2. Toxins e.g. Ricin
    • Chemotherapy delivered directly to cancerous cells
    • Diminishes off target effects
  3. Immunocytokines
  4. Bipolar mAbs
    • Specific for tumour cell as well as e.g. CTL
    • Brings these two things into contact
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the problems with antibody based immunotherapy?

A
  1. Specificity
    • Abs binding to non-tumour cells
  2. Penetration into large tumours
  3. Genetic instability of tumours
  4. Limited knowledge of dominant tumour Ags
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe Rituximab

A

Rituxan (Rituximab)
• Anti-CD20 Ab
• Depletes all B cells in the body through ADCC and C’-dep. cellular cytotoxicity

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

Describe Trastuzumab

A

Herceptin (trastuzumab)
• Anti-HER2
• HER2 is a GF receptor present in many breast cancers
• Blocks GF signalling, inhibiting growth of the tumour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe Bevacizumab

A 
Avastin (bevacizumab)
 • Anti-VEGF
 • VEGF is a GF for angiogenesis
 • mAb blocks angiogenesis, thus cutting off the blood supply to the tumour
 • esp. in colorectal cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe Brentuximab

A 
Adcetris (brentuzimab)
 • Anti-CD30
 • Antibody-drug conjugate
 • Targets CD30 on many lymphoma cells
 • Results in shrinkage of tumours in ALCL (anaplastic large cell lymphoma)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Give some examples of cytokine immunotherapy for cancer

List which cancers each can be used for, and the MOA

A

IL-2
• Melanoma, renal & colon cancer
• T and NK cell activation

IFNa
• Melanoma, lymphoma, renal cancer
• NK cell activation and increased MHC I expression

TNF
• Malignant ascites, sarcoma, melanoma
• Macrophage and lymphocytes activation

IL-12
• Melanoma
• NK and CTL activation

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

What are the problems associated with cytokine therapy?

A
  • AEs when administered systemically
  • Short half life
  • Limited success with some tumour types
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the approach of immunisation against tumours

Describe the effectiveness of such an approach

A

Approach:
• Patient immunised with killed tumour cells / purified tumour Ags
• + Adjuvant (e.g. BCG)

Results:
• Works in animals as prophylactic
• Often less effective therapeutically

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the problems associated with immunisation with tumour Ags?

A
  • Problems identifying the dominant tumour antigen

* Antigen modulation of tumour cells

17
Q

Describe adoptive cell therapy for cancer

What are the two approaches?

A
  1. Lymphocytes form blood or tumour infiltrate isolated from patient
  2. Lymphocytes expanded in culture with IL-2
  3. Lymphocytes transferred back into patient
  4. Hopefully, tumour regresses

Approaches:
1. LAK - Lymphokine activated killers
• Mainly NKs isolated from patient
• Limited success

  1. TIL - Tumour infiltrating lymphocytes
    • Lymphocytes taken from within / around tumour biopsy
    • This is more likely to include tumour specific CTLs and NKs
    • Dramatic improvements in some patients
18
Q

Why is autoimmunity often a good sign in cancer immunotherapy?

A

Indicates that the immune system has boosted its function

e.g. Vitiligo
• Immune system is destroying melanocytes
• Good indication in melanoma

19
Q

Describe the process of immunisation with immunogenically enhanced, viable tumour cells

A
  1. Tumour cells isolated from patient
  2. Tumour cells transfected with immunogenic molecules
    a. B7
    • B7 activates naïve T cells
    b. GM-CSF
    • Induces DC development
    • DCs mature and present tumour derive Ag to T cells in the lymphoid tissues
  3. Tumour cells put back into the patient
  4. Transfected cells capable of generating T cell responses
  5. T cell response directed against all tumour cells, not just those that were enhanced immunogenically
  6. Tumour shrinks
20
Q

Describe the rationale for ‘releasing the handbrake’ on the immune system

Describe how this can be done

A

Development of Tregs and expression of immunosuppressive cytokines ‘protects’ tumours from the immune system

Approaches:
1. Blocking CTLA-4
• Ipilimumab
• Blocks CTLA-4, the inhibitory molecule expressed by T cells
• T cells can no longer be inhibited
• Promising results in melanoma and prostate cancer patients

2. Depletion of Tregs
 • e.g. Ontak
 • IL-2-diptheria toxin conjugate
 • Binds and kills CD25+ Tregs
 • Mixed results in clinical trials
  1. Anti-PD-1
    • PD-1: programmed cell death protein 1
    • PD-1 expressed on T cells
    • When ligated by PD-L1 on tumour cells, T cells are inhibited
21
Q

Describe the function of B7?

A

Stimulates T cells through ligation of CD28

22
Q

What is the function of GM-CSF?

A

In this case, it recruits DCs to the environment (the tumour), enhancing T cell activation

MIIM30003 - Medical & Applied Immunology (30 decks)

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