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Foundations Exam 2 > Immunotherapy > Flashcards

Immunotherapy Flashcards

1
Q

Abscopal Effect

A

radiation to tumors is sometimes followed by reduction in size of tumors outside the radiation field

these off-targets effects may be related to immune activation

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2
Q

drugs in oncology that end in “-ib” are _____ while those ending in “-mab” are ____

A

“-ib” = small molecule inhibitor

“-mab” = monoclonal antibody

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3
Q

3 mechanisms of antibodies (and also mAb drugs)

A
  1. ADCC: antibody-dependent cellular cytotoxicity
  2. CDC: complement-dependent cytotoxicity
  3. ADCP: antibody-dependent cellular phagocytosis
  4. blocking receptors or ligands from binding
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4
Q

Rituximab targets ___

effect of this?

A

tu = tumor specific
xi = chimeric

Rituximab targets CD20 - expressed on all mature B cells (normal and malignant)

B cell death via ADCC and CDC

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5
Q

what kind of toxicity accompanies mAb therapy?

A

infusion reactions

cytokine release syndrome

immune suppression (off-target effect) - mAb targets healthy immune cells

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6
Q

Dinutuximab is a mAb that targets ___

effect of this?

A

tu = tumor specific
xi =chimeric

Dinutuximab targets GD2 - expressed on neuroblastoma cells and osteosarcoma cells

cell death via ADCC, CDC

*severe pain is a side effect because GD2 is also expressed on nerve endings

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7
Q

Trastuzumab is also known as

A

Herceptin

binds Her2 receptors in breast cancer

mAb, blocks growth signaling —> don’t kill cancer directly, block signaling pathway that supports cancer

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8
Q

What is the effect of Bevacizumab? What is its other name?

A

aka Avastin

mAb used in cancer treatment

binds VEGF-a (vascular endothelial growth factor A) —> decreases angiogenesis

*doesn’t kill cancer directly, but blocks pathways that support cancer

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9
Q

Blinatumumab is a _____antibody which binds _____

effect of this?

A

Blinatumumab is bispecific antibody —> binds CD19 (on most B-lineage leukemia) and CD3 (T cells)

brings CTL to malignant cells

BiTE: Bispecific T-cell Engaging Antibody

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10
Q

AFM13 is a ____ antibody that binds ____

effect of this?

A

AFM13: bispecific antibody, binds CD30 (on Hodgkin/ALCL) and CD16A (on NK, macrophage)

brings cytotoxic NK to malignant cell

BiNKE = Bispecific NK cell Engaging Antibody

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11
Q

Brentuximab vedotin is what kind of mAb treatment? What does it do?

A

Brentuximab vedotin: mAb (to CD30) covalently linked to toxic payload (microtubule disrupting agent)

protease-cleavable link between anti-CD30 mAb and microtubule-disputing agent allows for toxin release at appropriate destination

direct cytotoxicity

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12
Q

Gemtuzumab ozogamicin and
Inotuzumab ozogamicin are both _____ kinds of mAb

bonus: what are they used for?

A

monoclonal antibodies covalently linked to toxic payload

Gemtuzumab ozogamicin: anti-CD33, treats AML

Inotuzumab ozogamicin: anti-CD22, treats preB ALL

(there’s also Brentuximab vedotin, which is anti-CD30 and treats Hodgkin’s lymphoma)

hint: mAb with toxic conjugates have 2 words in their names (mAb + toxin)

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13
Q

for the drug pembrolizumab, what can you tell about it from its nomenclature?

A

pembrolizumab

pembro - li - zu - mab

li(m) = lymphocyte or immune modulating target

zu = humanized

mab = monoclonal antibody

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14
Q

for checkpoint inhibitors to work, you need a cancer with….

A

a high mutational burden (checkpoint inhibitors need a target)

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15
Q

how are CAR T cells created?

A

CAR = chimeric antigen receptor

  1. harvest lymphocytes from patient
  2. transfect with CAR construct
  3. reinfuse into patient following lymphodepletion (so T cells don’t attack CAR-T)
  4. CAR-T bind malignant target

result: improved T cell activation and proliferation

CAR-T cells proliferate (with CAR construct because they have been genetically modified)

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16
Q

what are the challenges of CAR-T therapy? (3)

A
  1. takes 6 weeks to create CAR T-cells
  2. cytokine release syndrome and neurotoxicity (can cross BBB)
  3. long-term efficacy and toxicity are unknown
17
Q

tisagenlecleucel is what kind of immunotherapy?

A

CAR (chimeric antigen receptor) T therapy

18
Q

name what kind of immunotherapies these are:
a. Rituximab
b. Blinatumumab
c. Brentuximab vedotin
d. Nivolumab
e. Tisagenlecleucel

A

a. Rituximab: mAb
b. Blinatumumab: bi-specific anitbody
c. Brentuximab vedotin: antibody-drug conjugate
d. Nivolumab: checkpoint inhibitors
e. Tisagenlecleucel: CAR-T

19
Q

this chimeric mAb targets CD20 present on mature B cells (normal and malignant)

What is?

A

Rituximab - causes cell death via ADCC and CDC (complement-dependent cytotoxicity)

20
Q

This mAb is used against sarcomas. It binds GD2 expressed in neuroblastoma and osteosarcoma. However, severe pain is a side effect. What is?

A

Dinutuximab - causes cell death via ADCC and CDC

severe pain is a side effect of Dinutuximab because GD2 is also expressed on peripheral nerve endings

21
Q

Trastuzumab and Bevacizumab have [direct/indirect] effect on cancer cell death

A

Trastuzumab = Herceptin (binds Her2 on breast cancer)

Bevacizumab = Avastin (binds VEGF-A)

both have indirect effects on cancer cell death by blocking pathways that support cancer growth (rather than direct cell killing)

22
Q

Herceptin is also known as

what does it do

A

Trastuzumab: Her2 receptor antagonist (breast cancer, stops growth signaling)

23
Q

Avastin is also known as

what does it do

A

Bevacizumab: binds VEGF-A (decreases angiogenesis)

used in cancer immunotherapy

24
Q

this BiTE binds CD19 and CD3

What is BiTE, where are these cell surface proteins found, what is this drug, and what is its effect?

A

BiTE = BIspecific T-cell Engaging Antibody

Blinatumumab: binds CD19 (B-lineage leukemia) and CD3 (T cells) —> brings CTL to cancer

25
Q

this BiNKE bidns CD30 and CD16A

what is BiNKE, where are these cell surface proteins found, what drug is this, and what is its effect?

A

BiNKE = BIspecific NK cell Engaging antibody

AFM13: binds CD30 (Hodgkin/ALCL) and CD16A (NK, macrophages) —> brings cytotoxic NK to cancer

[ALCL = anaplastic large cell lymphoma, type of non-Hodgkin lymphoma)

26
Q

what antibody-drug conjugate binds CD30 found in Hodgkin lymphoma?

A

Brentuximab vedotin: antiCD30 mAB + microtubule disrupting agent

27
Q

Nivolumab and Ipilimumab are immunotherapy mAb targeted at checkpoint inhibitors. What does each bind?

A

Nivolumab: binds PD-1 receptor, blocks interaction with PD-L (programmed death ligand)
*PD-1 receptor activation inhibits T cells, so Nivolumab prevents T cell inhibition

Ipilimumab: binds CTLA-4 (present on activated T cells) to prevent CTLA-4 inhibition of T cells

28
Q

this checkpoint inhibitor binds PD-1 receptor, blocks interaction with PD-L (programmed death ligand)

what is? and how does this help kill cancer?

A

Nivolumab

*PD-1 receptor activation inhibits T cells, so Nivolumab prevents T cell inhibition

29
Q

this checkpoint inhibitor binds CTLA-4 (present on activated T cells) to prevent CTLA-4 inhibition of T cells

what is?

A

ipilimumab

30
Q

which of these targets GD2 expressed on neuroblastoma and osteosarcoma?
a. rituximab
b. nivolumab
c. tisagenlecleucel
d. dinutuximab

A

d. dinutuximab targets GD2 —> cell death via ADCC and CDC

*note severe pain is side effect, GD2 is also expressed on peripheral nerve endings

31
Q

which of these is the other name for Avastin, which binds VEGF-A?
a. trastuzumab
b. nivolumab
c. bevacizumab
d. blinatumumab

A

c. bevacizumab = avastin

32
Q

which of these is a BiTE, which is a BiNKE?
a. blinatumumab
b. AFM13

what do they bind?

A

a. blinatumumab: Bispecific T cell Engaging antibody (BiTE), binds CD19 (B cell leukemia) and CD3 (T cells)

b. AFM13: Bispecific NK cell Engaging antibody (BiNKE), binds CD30 (Hodgkin/ ALCL) and CD16A (NK, macrophage)

33
Q

which of these are checkpoint inhibitors?
a. brentuximab
b. bevacizumab
c. rituximab
d. nivolumab
e. tisagenlecleucel
f. ipilimumab

what do they bind?

A

d. nivolumab: binds Programmed Death receptor (prevents PD-L binding, which inhibits T cells)

f. ipilimumab: binds CTLA-4 on T cells (which binds B7 on DC to inhibit T cells)

Foundations Exam 2 (42 decks)

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