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BMSC2210 - Chemotherapy > L16 - Anti-cancer 4: therapeutic antibodies, biological therapies & new directions > Flashcards

L16 - Anti-cancer 4: therapeutic antibodies, biological therapies & new directions Flashcards

1
Q

How can humanised antibodies be used in anti-cancer treatment ( what does the binding of the antibody do)?

A

binding of antibody - prevent interaction with cell-surface receptor OR recruit immune cells to kill antibody-bound cancer cells

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2
Q

What can be conjugated to humanised antibodies?

A

toxin

radioisotope - local source of radiotherapy

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3
Q

What are the 2 criteria for antigen target for humanised antibodies?

A

protein over-expressed on tumour cell surface

low level/absent in normal cells

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4
Q

Why does the monoclonal antibody have to be humanised?

A

immune system would recognise as foreign if not

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5
Q

How are humanised antibodies produced?

A

recombinant DNA technology

keep original CDR region but make the rest human

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6
Q

What are the new developments that make antibody fragments that penetrate tissues better?

A

single chain variable region fragments (scFv)

synthesised in bacteriophage

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7
Q

What are scFv antibodies?

A

single chain variable region fragments

variable region connected by by linker

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8
Q

Where are scFv displayed?

A

pIII of a filamentous phage

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9
Q

How are particular scFv antibodies expanded?

A

panning

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10
Q

Clinical potential of humanised monoclonal antibodies?

A

huge table on slide

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11
Q

are monoclonal antibodies just used for cancer?

A

NO

e.f. anti-TNFa - rheumatoid arthritis

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12
Q

What us Herceptin used to treat?

A

breast cancers that DO NOT EXPRESS estrogen/progesterone receptor

OR

DO NOT respond to tamoxifen

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13
Q

What does Herceptin target?

A

HER2

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14
Q

Is HER2 over-expressed in breast cancer?

A

yes, 30%

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15
Q

When is Herceptin most effective?

A

metastatic breast cancer

not so much in early stages

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16
Q

Can Herceptin be used in combined therapy?

A

yes, with paclitaxel

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17
Q

Advserse effects of Herceptin?

A

heart failure

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18
Q

New development with Herceptin?

A

link emtansine to Herceptin

tubulin inhibitor usually too toxic for cells

break off from herceptin at breast cancer cells - very toxic

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19
Q

What is Bevacizumab also known as?

A

Avastin

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20
Q

What is Bevacizumab given with in colorectal cancer?

A

5FU

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21
Q

What does bevacizumab do?

A

stops new blood vessels forming

binds to VEGF

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22
Q

adverse effects of bevacizumab?

A

hypertension

intestinal bleeding

interferes with normal blood vessels

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23
Q

What does Rituximab do?

A

binds CD20 expressed on B cells

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24
Q

What is rituximab used to treat?

A

non-Hodgkin lymphoma

other lymphoma/leukaemia

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25
Q

What is rituximab given with?

A

other anti-cancer drugs

cyclophosphamaide

26
Q

side effects of rituximab?

A

hypotension

cardiac problems

27
Q

What does Cetuximab do?

A

target EGF receptor

interfere with cancer cell growth, prevent EGF binding

28
Q

What is cetuximab given with?

A

Irinotecan

29
Q

What is Cetuximab used for?

A

colorectal cancer

30
Q

side effects of cetuximab?

A

fever

hypotension

31
Q

What is CTLA-4?

A

cytotoxic T cell antigen 4

negative molecule, downregulates immune response

can engage with CD80/86 on cancer cell instead of CD28

32
Q

What happens when CD28 binds to CD80/86 on cancer cell?

A

completel activation and priming

costimulation of immune response against cancer cells

33
Q

What is the name for Anti-CTLA-4?

A

Iplilumumab

34
Q

What is Ipilumumab?

A

fully humanised MoAb

blocks CTLA-4

activates Cytotoxic T cells

35
Q

What are Anti-CTLA4 MoAbs also referred to as?

A

immune checkpoint inhibitors

36
Q

What does Ipilumumab treat?

A

melanoma

37
Q

What does PD-1 do?

A

induce apoptosis of T cells

if PD-1 engages with ligand - kills T cells

38
Q

Do cancer cells overexpress PD-1?

A

yes - to kill T cells

39
Q

What is the FULLY humanised MoAb against PD-1?

A

MDX1106

40
Q

What are the humanised MoAbs that block PD-1?

A

Nivolumab

Pembrolizumab

41
Q

What is IMA901?

A

synthetic RCC-associated peptides

stimulate T cells

42
Q

What is AGS003?

A

patient DCs loaded with autologous tumour RNA

stimulate CD28+ memory T-cells

43
Q

What are immunotherapy approaches to RCC?

A 
MDX1106
nivolumab
pembrolizumab
IMA901
AGS003
44
Q

What is L-Asparaginase?

A

Bacterial enzyme

depletes blood asparagine - affects tumour cells that have low asparagine

45
Q

What is L-asparaginase used for?

A

childhood acute lymphocytic leukaemia

46
Q

What is L-asparaginase used in combo with?

A

vincristine

prednisone

47
Q

Do cancer cells have high levels of asparagine?

A

NO - low levels

48
Q

What are the 2 types of IFNs?

A

Type 1 - alpha and beta

Type 2 - gamma

49
Q

What were IFNs originally discovered for?

A

anti-virals

50
Q

What 2 things do IFNs do against cancer cells?

A

promote apoptosis in cancer cells

stimulate immune cells to recognise/kill cancer cells

51
Q

What does IFNs are approved for viral cancers?

A

IFN-alpha2a
IFN-alpha2b

AIDS-related KSHV

hairy cell leukaemia (retrovirus)

52
Q

How many human IFN-a genes?

A

at least 12

53
Q

side effects of high dose IFN?

A

depression

loss of energy

54
Q

What does IFN-a2 extend disease-free survial for?

A

melanoma

after surgical removal of tumour

55
Q

What is IL-2?

A

T-lymphocyte growth factor

56
Q

What is IL-2 used to treat?

A

RCC and melanoma

57
Q

What is IL-2 possibly synergistic with?

A

IFN-a2

greater effects used together

58
Q

Side effects of IL-2?

A

hypotension
liver damage
max tolerance 14 doses

59
Q

What is GM-CSF used for?

A

reconstitute myeloid blood cells after HSCT

60
Q

How can GM-CSF be useful in cancer treatment?

A

stimulate cellular immune system

synergistic with IL-12 stimulation of immune cells

61
Q

How does IL-12 help cancer treatment?

A

Stimulate B-cells, T-cells and NK cells

acts as IMMUNOSTIMULANT

BMSC2210 - Chemotherapy (17 decks)

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