Immunotherapy Flashcards
Abscopal Effect
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
drugs in oncology that end in “-ib” are _____ while those ending in “-mab” are ____
“-ib” = small molecule inhibitor
“-mab” = monoclonal antibody
3 mechanisms of antibodies (and also mAb drugs)
- ADCC: antibody-dependent cellular cytotoxicity
- CDC: complement-dependent cytotoxicity
- ADCP: antibody-dependent cellular phagocytosis
- blocking receptors or ligands from binding
Rituximab targets ___
effect of this?
tu = tumor specific
xi = chimeric
Rituximab targets CD20 - expressed on all mature B cells (normal and malignant)
B cell death via ADCC and CDC
what kind of toxicity accompanies mAb therapy?
infusion reactions
cytokine release syndrome
immune suppression (off-target effect) - mAb targets healthy immune cells
Dinutuximab is a mAb that targets ___
effect of this?
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
Trastuzumab is also known as
Herceptin
binds Her2 receptors in breast cancer
mAb, blocks growth signaling —> don’t kill cancer directly, block signaling pathway that supports cancer
What is the effect of Bevacizumab? What is its other name?
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
Blinatumumab is a _____antibody which binds _____
effect of this?
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
AFM13 is a ____ antibody that binds ____
effect of this?
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
Brentuximab vedotin is what kind of mAb treatment? What does it do?
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
Gemtuzumab ozogamicin and
Inotuzumab ozogamicin are both _____ kinds of mAb
bonus: what are they used for?
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)
for the drug pembrolizumab, what can you tell about it from its nomenclature?
pembrolizumab
pembro - li - zu - mab
li(m) = lymphocyte or immune modulating target
zu = humanized
mab = monoclonal antibody
for checkpoint inhibitors to work, you need a cancer with….
a high mutational burden (checkpoint inhibitors need a target)
how are CAR T cells created?
CAR = chimeric antigen receptor
- harvest lymphocytes from patient
- transfect with CAR construct
- reinfuse into patient following lymphodepletion (so T cells don’t attack CAR-T)
- 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)
what are the challenges of CAR-T therapy? (3)
- takes 6 weeks to create CAR T-cells
- cytokine release syndrome and neurotoxicity (can cross BBB)
- long-term efficacy and toxicity are unknown
tisagenlecleucel is what kind of immunotherapy?
CAR (chimeric antigen receptor) T therapy
name what kind of immunotherapies these are:
a. Rituximab
b. Blinatumumab
c. Brentuximab vedotin
d. Nivolumab
e. Tisagenlecleucel
a. Rituximab: mAb
b. Blinatumumab: bi-specific anitbody
c. Brentuximab vedotin: antibody-drug conjugate
d. Nivolumab: checkpoint inhibitors
e. Tisagenlecleucel: CAR-T
this chimeric mAb targets CD20 present on mature B cells (normal and malignant)
What is?
Rituximab - causes cell death via ADCC and CDC (complement-dependent cytotoxicity)
This mAb is used against sarcomas. It binds GD2 expressed in neuroblastoma and osteosarcoma. However, severe pain is a side effect. What is?
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
Trastuzumab and Bevacizumab have [direct/indirect] effect on cancer cell death
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)
Herceptin is also known as
what does it do
Trastuzumab: Her2 receptor antagonist (breast cancer, stops growth signaling)
Avastin is also known as
what does it do
Bevacizumab: binds VEGF-A (decreases angiogenesis)
used in cancer immunotherapy
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?
BiTE = BIspecific T-cell Engaging Antibody
Blinatumumab: binds CD19 (B-lineage leukemia) and CD3 (T cells) —> brings CTL to cancer
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?
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)
what antibody-drug conjugate binds CD30 found in Hodgkin lymphoma?
Brentuximab vedotin: antiCD30 mAB + microtubule disrupting agent
Nivolumab and Ipilimumab are immunotherapy mAb targeted at checkpoint inhibitors. What does each bind?
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
this checkpoint inhibitor binds PD-1 receptor, blocks interaction with PD-L (programmed death ligand)
what is? and how does this help kill cancer?
Nivolumab
*PD-1 receptor activation inhibits T cells, so Nivolumab prevents T cell inhibition
this checkpoint inhibitor binds CTLA-4 (present on activated T cells) to prevent CTLA-4 inhibition of T cells
what is?
ipilimumab
which of these targets GD2 expressed on neuroblastoma and osteosarcoma?
a. rituximab
b. nivolumab
c. tisagenlecleucel
d. dinutuximab
d. dinutuximab targets GD2 —> cell death via ADCC and CDC
*note severe pain is side effect, GD2 is also expressed on peripheral nerve endings
which of these is the other name for Avastin, which binds VEGF-A?
a. trastuzumab
b. nivolumab
c. bevacizumab
d. blinatumumab
c. bevacizumab = avastin
which of these is a BiTE, which is a BiNKE?
a. blinatumumab
b. AFM13
what do they bind?
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)
which of these are checkpoint inhibitors?
a. brentuximab
b. bevacizumab
c. rituximab
d. nivolumab
e. tisagenlecleucel
f. ipilimumab
what do they bind?
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)
