Anti-tumour Immunity And Immunotherapy For Cancer

Question 1

Which tumours does immunodeficiency lead to?

Answer 1

Kaposi sarcoma and lymphoma

Question 2

What does tumour immunosurveillance describe?

Answer 2

A process where the immune system continually recognises cancerous and pre-cancerous cells leading to their elimination

Question 3

What are the three phases of immunoediting?

Answer 3

Elimination
Equilibrium
Escape

Question 4

What cells are involved in the elimination phase of immunoediting?

Answer 4

NK, NKTs, macrophages and dendritic cells

Question 5

What chemicals lead to tumour death?

Answer 5

INFgamma and chemokines

Question 6

What happens in the elimination phase of immunoediting?

Answer 6

Tumour specific dendritic cells activate adaptive immunity to drain lymph nodes
Tumour specific CD4+ and CD8+ T cells join to clear the tumour

Question 7

When does the equilibrium phase happen?

Answer 7

If the elimination phase is incomplete

Question 8

What happens in the equilibrium phase of immunoediting?

Answer 8

Tumour cells lie dormant and may modulate tumour antigen expression and stress signals

Question 9

What is tumourigenesis?

Answer 9

Normal cells undergoing change develops tumour antigens

Danger signals such as extracellular matrix products can be detected by the immune system

Question 10

How does the BCG vaccine help with bladder cancer?

Answer 10

Involves DC activation
Direct NK activation
Bystander T cell activation

Question 11

What are type 1 interferons produced by?

Answer 11

Virally infected cell

Question 12

What do type 1 interferons do?

Answer 12

Upregulates MHC class1, tumour antigens and adhesion molecules
Activates T cells, B cells and dendritic cells

Question 13

What is type 1 interferon used in the treatment of?

Answer 13

Metastatic melanoma

Question 14

What is a T cell growth factor?

Answer 14

Interleukin-1

Question 15

What is interleukin-1 used for?

Answer 15

Renal cell carcinoma and melanoma

Question 16

What are LAK cells?

Answer 16

PBMC treated with IL-2 and re-infused into patients

Question 17

What does GM-CSF do?

Answer 17

Stimulates APCs

Question 18

What can GM-CSF be used to treat?

Answer 18

Melanoma

Question 19

What ways can antibodies affect tumour growth?

Answer 19

Direct tumour cell killing
Immune-mediated tumour cell killing
Vascular and stromal cell ablation

Question 20

How does antibody direct tumour cell killing work?

Answer 20

Antibodies block receptors and enzymes so they’re conjugated to toxins

Question 21

How does immuno mediated direct tumour cell killing work?

Answer 21

Antibodies binding to cell surface of tumour cell exposes fc portion of the fc receptors on macrophages which then destroy the cell

Question 22

What is vascular and stromal cell ablation?

Answer 22

Removal/destruction of vascular and stromal cells to prevent growth of tumour

Question 23

What blocks ERBB2 signalling?

Answer 23

Herceptin

Question 24

What does avastin target?

Answer 24

VEGF and blocks signalling

Question 25

What is avastin used against?

Answer 25

Colon cancer NSCLC Gliblastoma Kidney cancer

Question 26

What is rituximab used for?

Answer 26

Anti-CD20 used for CD20 positive B cell non-Hodgkin lymphoma and chronic lymphocytic lymphoma

Question 27

What is alemtuzumab?

Answer 27

AntiCD52

Question 28

What is alemtuzumab used for?

Answer 28

B-CLL

Question 29

How does ipilimumab work?

Answer 29

Blocks the inhibition of CTLA-4 signalling

Question 30

What is ipilimumab used in?

Answer 30

Metastatic melanoma

Question 31

What are the ways in which immunotherapy drugs can be delivered?

Answer 31

90-yttrium labelled ibritumomab tiuxetan Brentuximab vedotin Ontak

Question 32

How does 90-yttrium labelled ibritumomab tiuxetan work?

Answer 32

Antibody to CD20 delivering radiotherapy to follicular B cell non-Hodgkin lymphoma

Question 33

How does brentuximab vedotin work?

Answer 33

Antibody to CD30 delivering MMAE

Question 34

How does Ontak work?

Answer 34

IL-2 delivering diphtheria toxin in T cell lymphoma

Question 35

How does checkpoint inhibition work?

Answer 35

Antibody against PD-1

Question 36

What are the cell based therapies for cancer?

Answer 36

LAK, NK-T, gamma delta T cells | Dendritic cells

Question 37

What does LAK stand for?

Answer 37

Lymphokine activated killers

Question 38

How does LAK cell therapy work?

Answer 38

PMBCs taken from patients and cultured with IL-2 in vitro | Causes formation of NK cells which then have higher than normal anti-tumour activity

Question 39

What do NK cells recognise?

Answer 39

Lack of MHC-1

Question 40

What are NK-T cells used for?

Answer 40

In vitro expanded NKT based vaccines

Question 41

What is the main cell type of NK cells?

Answer 41

LAK populations

Question 42

What are the gamma delta T cells structurally similar to?

Answer 42

Alpha beta cells

Question 43

What may the gamma delta T cells not need?

Answer 43

Normal antigen presentation mechanisms | Recognise peptides and therefore no need for protein processing

Question 44

What do gamma delta T cells recognise/respond to?

Answer 44

Respond to MICA and MICB expressed on stressed cells and recognise small organic molecules secreted by bacteria

Question 45

How do you derive dendritic cells for cell based cancer therapy?

Answer 45

``` Isolate monocytes from a patient Derive them into immature dendritic cells using GM-CSF and IL-4 Load DCs with a tumour antigen Mature DCs into APCDCs Put back into patient ```

Question 46

What is the prognosis if lymphocytes are seen in a tumour?

Answer 46

Good

Question 47

What is the prognosis if there is a high CD8+/Treg ratio?

Answer 47

Higher

Question 48

What has pre-existing antigen specificity of TILs been correlated with?

Answer 48

Outcome in immunotherapy on melanoma

Question 49

What is the method for adoptive cell therapies with TILs?

Answer 49

Tumour biopsy In vitro polyclonal stimulation Lymphodeletion of patient Stimulated T cells reintroduces into the patient

Question 50

What are the results of adoptive cellular therapy with TILs?

Answer 50

Cytotoxicity against tumour cells culture | Homing of transferred T cells to tumour in vivo

Question 51

When do you get the best results for adoptive cellular therapy with TILs?

Answer 51

Patients are pre-treated with peripheral lymphodeletion regimen of total body irradiation

Question 52

What are the disadvantages of adoptive cellular therapy with TILs?

Answer 52

Need enough tumour to generate sufficient CTLs TILs may be refractory to stimulation Time consuming and labour intensive (requires infrastructure) Culture time may be too long or influence the quality of T cells High failure rate of culture

Question 53

What does CAR stand for?

Answer 53

Chimeric antigen receptors

Question 54

What is CAR composed of?

Answer 54

Antibody recognition domains | Cytoplasmic tail with multiple signalling domains that activate T cells

Question 55

What are the advantages of CAR?

Answer 55

Specificity and high affinity

Question 56

What is the point of theraputic vaccination?

Answer 56

To induce a long lasting response against tumour Stimulate the adaptive arm of the immune response Use professional APC such as dendritic cells

Question 57

What happens in high affinity TCR transduction?

Answer 57

TCRs reactive to TAAs are characterised and cloned Alpha and beta chains of TCR are engineered into retro viral vector Patients CD8+ T cells from peripheral blood are removed and transducers with TCR virus Adoptive transfer back into patients

Question 58

What are the issues with high affinity TCR transduction?

Answer 58

Initial results -> 2/15 patients with clinical response T cells remain in peripheral blood for up to one year Epitopes need to be characterised and matched to HLA Must be present in the tumour Becomes a patient specific therapy