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Biotherapeutics > Checkpoint Inhibitors > Flashcards

Checkpoint Inhibitors Flashcards

1
Q

What characteristic of trastuzumab have to allow for infrequent dosing?

A

Long serum half life

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2
Q

What is the loading dose of trastuzumab?

A

8mg per kg followed by 6mg per kg (IV) over a 90min period every 3rd week

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3
Q

Can you effectively clear solid tumours?

A

No there is always minimal residual disease

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4
Q

What are 3 reasons for trastuzumab resistance?

A

steric effects
alternative elevations of other receptor tyrosine kinases
intracellular alterations

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5
Q

What does KEYTRUDA target?

A

The immune system

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6
Q

What are the 6 OG hallmarks of cancer?

A

Sustaining proliferative signaling
evading growth suppressors
activating invasion & metastasis
enabling replicative immortality
inducing angiogenesis
resisting cell death

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7
Q

What does the APC do?

A

Recognise tumour cell

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8
Q

What are 4 ways tumours can evade the immune system?

A

Inhibition of APC
Dysregulation of immune cell activity
secretion of immunosuppressive factors
recruitment of immunosuppressive cell type

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9
Q

What are 2 emerging hallmarks?

A

Deregulating cellular energetics
avoiding immune destruction

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10
Q

What are 2 enabling characteristics of the new hallmarks?

A

Genome instability & mutation
Tumour promoting inflammation

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11
Q

What regulates cell cycle?

A

Cyclin

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12
Q

What is the survival of tumours assisted by?

A

Checkpoint immunomodulation to maintain imbalance between immune surveillance & cancer cell proliferation

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13
Q

What are 3 checkpoint antibody inhibitors?

A

anti-CTLA-4
anti-PD-1
anti-PD-L1

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14
Q

Is the antigen + MHC only being presented to a TCR sufficient for T cell proliferation?

A

No - need B7 & CD28 costimulation

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15
Q

What 2 checkpoint molecules abrogate T cell responses?

A

PD-1
CTLA-4

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16
Q

What does antibody blockade of immune checkpoints enhances?

A

T cell responses

17
Q

What cytokine is produced to lead to PDL-1 expression on tumour cells?

A

IFN-gamma

18
Q

Which type of antibody is showing most progress for checkpoint therapy?

A

Blocking antibodies

19
Q

What is the MoA of inhibitory receptors?

A

regulate CTL activation & effector functions to sustain self-tolerance & minimize bystander tissue damage

20
Q

What was the furst immune checkpoint inhibitor?

A

Ipilimumab as an anti CTLA-4 antibody for melanoma

21
Q

What are the 2 classes of immunotherapy that is FDA approved?

A

PD-1 inhibitor
CTLA-4 inhibitor

22
Q

Whats an example of an Anti-PD1 drug?

A

Nivolumab

23
Q

What is an example of an anti-PD-L1?

A

Avelumab

Biotherapeutics (3 decks)

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