CanImmun

Question 1

What are the 3 phases of immunoediting?

Answer 1

→Elimination
→Equilibrium
→Escape

Question 2

What danger signals are expressed on tumour cells?

Answer 2

→MICA an ULBP

→RAE1

Question 3

What are MICA/B recognised by?

Answer 3

→gamma delta cells which express NKG receptors

Question 4

Which innate cells are involved in the elimination phase of immunoediting?

Answer 4

→NKs
→NKTs
→Macs
→DCs
→Tumour specific CD4+ and CD8+ T cells

Question 5

What signals lead to tumour death in elimination?

Answer 5

→INF-gamma

→chemokines

Question 6

How do tumour cells hide from immune system?

Answer 6

→modulate MICA/B

Question 7

How does BCG act as a cancer immunotherapy?

Answer 7

→Stimulates the innate immune system TLRs

Question 8

What cancers is BCG used for?

Answer 8

→bladder cancer- intravessicular injection

Question 9

What is BCG vaccine originally for?

Answer 9

→TB

Question 10

Which pathogens produce Type 1 interferon alpha and beta?

Answer 10

→virus

Question 11

How does Type 1 inteferon work as cancer immunotherapy?

Answer 11

→Upregulates MHC Class 1, increased expression tumour antigens and adhesion molecules
→Activates T cells, B cells and DC

Question 12

What are the side effects of interferon cancer use?

Answer 12

→flu-like symptoms

Question 13

How is interleukin-2 used for cancer therapy?

Answer 13

→T cell growth factor

→Success in RCC(renal cell carcinoma) and melanoma

Question 14

How is the toxicity of interleukin cancer use mediated?

Answer 14

→LAK cells, PBMC treated with IL-2 and re-infused into patients

Question 15

How is GM-CSF used in cancer therapy?

Answer 15

→stimulates APC

→benefit if used in conjunction with IL-2

Question 16

How are Abs used in cancer therapy?

Answer 16

→direct ymour cell killing
→activate phagocytosis, complement, and ADCC
→vascular and stomal cell ablation
→anti-CTLA4
→cross presentation and Tcell actiavtion

Question 17

How does Trastuzumab work in breast cancers?

Answer 17

→targets ERBB2 (human epidermal growth factor) on breast cancer cells.

→Blocks ERBB2 signalling and allows targeting of ADCC

Question 18

How does Bevacizumab(Avastin) work as cancer therapy?

Answer 18

→targets VEGF and blocks signalling

Question 19

Give examples of drugs that induce apoptosis

Answer 19

→Rituximab: anti-CD20
→Alemtuzumab (Campath): anti CD52

→Target all Bcells

Question 20

What cancer is anti-CTLA4 used for?

Answer 20

→metastatic melanoma

Question 21

What are some delivery cancer therapy methods?

Answer 21

→90Yttrium-labelled ibritumomab tiuxetan. Antibody to CD20 delivering radiotherapy to follicular B-cell NHL

→Brentuximab vedotin: antibody to CD30 delivering toxin (Aurostatin) to CD30+ B cells in NHL

→Ontak: IL-2 delivering diphtheria toxin in T cell lymphoma

Question 22

What are some checkpoint inhibition therapies?

Answer 22

→Blockade of effector cell death

→Antibody against PD-1 (programmed cell death protein 1)

Question 23

What are some cell based therapies for cancer?

Answer 23

→LAK
→NK-T cells
→gd T cells
→DC
→TIL
→CAR

Question 24

What are LAK cells?

Answer 24

→Lymphokine Activated Killers

→NK, NKT and T cells (CD25+)

→Predominantly NK cells

→Can target NK resistant tumour cells

Question 25

What markers are NK cells positive for?

Answer 25

→CD3- CD56+
→ subsets CD56 bright and CD56 dim

→CD16+/CD16- (FcRIII)

Question 26

Where are NK cells predominantly found?

Answer 26

→blood
→BM
→liver
→spleen

Question 27

What is involved in NK-T immunotherapy?

Answer 27

→a-galactosyl ceramide

Question 28

What do gamma-delta Tcells respond to?

Answer 28

→MICA and MICB expressed on stressed cells

→small organic molecules secreted by bacteria: eg HMBPP ((E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate) from mycobacteria

→May not need normal antigen presentation mechanisms

→Single cell type most favourably good outcome

Question 29

What cells does therapeutic vaccination use?

Answer 29

→APCs

Question 30

What are the principles of DC vaccination for cancer therapy?

Answer 30

→DCs are extracted from patients and then exposed to either digested tumor peptides or messenger RNA from the patient’s autologous tumor

→ The DCs are then transfused back into the patient, primed and ready to activate immune responses

Question 31

What are TILs?

Answer 31

→recognize and kill cancer cells

Question 32

What is adoptive cellular therapy?

Answer 32

→Tumour biopsy

→In vitro polyclonal stimulation (IL-2 and anti-CD3 antibody) to expand and then put back into patient

→Best results when patients are pre-treated with peripheral lymphodepletion regimen of total body irradiation

Question 33

What are the disadvantages of TIL adoptive cell therapy?

Answer 33

→Need enough tumour to generate sufficient CTLs

→TILs may be refractory to stimulation (about 30%)

→Time consuming and labour intensive – requires infrastructure.

→Culture time may be too long for patients

→Culture time MAY influence quality of T cells- the longer Tcells are maintained in culture, the less specific they become.

→High failure rate of culture.

Question 34

What is ACT using peripheral blood Tcells?

Answer 34

→Clonal expansion against a known antigen
→easy availability of large numbers of T cells
Peripheral blood contains many precursors with TAA reactivity

Question 35

What is high affinity TCR transduction for cancer therapy?

Answer 35

→Alpha and beta chains of TCR are engineered into a retroviral vector.

→Patient’s CD8+ T cells from peripheral blood are removed and transduced with TCR-virus.

→Adoptive transfer back into patients

→Engineering Tcell specific to tumour antigen

Question 36

What is CART?

Answer 36

→Similar in nature to TCR transgenics, but NOT MHC restricted

→CARs are designed to allow the T cells to attach to specific proteins on the surface of the cancer cells