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Therapeutics IV > Oncology Immunotherapy_Edit > Flashcards

Oncology Immunotherapy_Edit Flashcards

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1
Q

What is Coley’s toxin (aka MBV)?

A

First attempt to use immunotherapy and hyperthermia against cancer

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2
Q

Define positive selection

A

permits the survival of only those T-cells whose TCRs are capable of recognizing self-MHC molecules

responsible for the CREATION OF A SELF-MHC-RESTRICTED REPERTOIRE OF T-CELLS

cells that fail positive selection are eliminated within the thymus by apoptosis

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3
Q

Define negative selection

A

eliminates T cells that react too strongly with self-MHC or with self-MHC plus self-peptides

bearing high-affinity receptors for self-MHC molecules alone or self-antigen presented by self-MHC, which results in self-tolerance

extremely important factor in GENERATING A PRIMARY T-CELL REPERTOIRE THAT IS SELF-TOLERANT

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4
Q

Antibody production is the

A

humoral arm of the immune system

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5
Q

substem of all monoclonal antibodies

A

-mab

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6
Q

substem of mouse antibody

A

-o

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7
Q

substem of chimeric antibody

A

-xi

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8
Q

substem of humanized antibody

A

-zu

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9
Q

substem of fully human antibody

A

-u

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10
Q

What is genomically amplified in breast cancer

A

Her2 (overexpressed in 25 - 30% of all breast cancers)

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11
Q

Trastuzumab specific for

A

Her2

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12
Q

Trastuzumab indication

A

tx of breast cancer that overexpress Her2

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13
Q

Pertuzumab specific for

A

Her2

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14
Q

Pertuzumab capable of

A

binding to Her2 and INHIBITING DIMERIZATION

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15
Q

Pertuzumab used in combination with

A

Trastuzumab

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16
Q

Pertuzumab indicated

A

in combination with trastuzumab and docetaxel for tx of patients with Her2-positive metastatic breast cancer (MBC) who have not received prior anti-Her2 therapy or chemotherapy for metastatic disease

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17
Q

Can pertuzumab be used at home

A

NO

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18
Q

Which domains do trastuzumab and pertuzumab bind to?

A

T = 4

P = 2

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19
Q

Margetuximab

A

showed slightly better survival in pretreated patients as compared to trastuzumab (SOPHIA trial). Approved in December 2020

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20
Q

Cetuximab binds to

A

EGF receptor

competitively inhibits binding of EGF and TGF-alpha

blocks phosphorylation and activation of receptor-associated KINASES

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21
Q

Cetuximab primary indication

A

tx of colorectal and head and neck cancers

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22
Q

What SE associated with EGFR-inhibition

A

anciform rash

associated with positive disease response

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23
Q

Panitumumab binds

A

binds to domain of EGF receptor

competitively inhibits binding of EGF and TGF-alpha

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24
Q

Panitumumab indication

A

tx of colorectal cancer

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25
Explain two-tiered targeting affect of antibody therapy as compared to small molecule kinase inhibitors
In general antibodies bindings to their targets on the surface of tumor cells will inhibit the function of that molecule. This along with activation of the ADCC can lead to differential therapeutic outcomes when using antibodies as compared to the small molecules.
26
Describe why the combined use of pertuzumab and trastuzumab both defies and complies with general rules of combination therapy
Against: Shared target equals shared toxicities. For: Different bindings sites on HER2, different mechanisms of HER2 inhibition, enhanced activation of the ADCC
27
Administration of cetuximab and panitumumab for the tx of metastatic colorectal cancer now requires
KRAS mutational status
28
CD20 works with
the B-cell receptor (BCR) to drive proliferation of B-cells
29
CD20 also plays a role in
the proliferation of B-cell lymphomas
30
Ofatumumab is specific for
CD20
31
CD20 is expressed by normal
B lymphocytes and immature pre-B cells
32
Ofatumumab indication
is in the tx of B-cell non-Hodgkin's lymphoma
33
Bevacizumumab specific for
vascular endothelial growth factor (VEGF)
34
Bevacizumumab fact
no evidence of efficacy as a single agent
35
Bevacizumumab used in combination with (indication)
5-FU based chemotherapy for FIRST-LINE tx of metastatic colorectal cancer
36
Bevacizumumab binds the ______ while ramucirumab binds the _________
ligand; receptor
37
What is Trastuzumab Emtansine?
Antibody-drug conjugate consisting of the cytoxic agent linked to the monoclonal antibody trastuzumab
38
Trastuzumab binds to
Her2/Neu receptor and leads to usual herceptin response
39
Emtansine does what
enters cells and inhibits microtubule assembly emtansine toxicity significantly reduced because of Her2 targeting
40
Trastuzumab Emtansine indication
2nd line tx for Her2-positive metastatic breast cancer
41
Trastuzumab conjugated with what other drugs
deruxtecan the "tecans" are TOPOI inhibitors
42
Describe Lymphomas
arise from cells that populate lymph notes i.e. hodgkin's lymphoma (locate reed-sternberg cells)
43
Brentuximab vedotin is a
anti-CD30 antibody conjugated to monomethyl auristatin E (MMAE)
44
Reed-sternberg cells associated with
lymphomas
45
Reed-sternberg cells express
CD30
46
What is MMAE
a microtubule destabilizing agent, ~200 times more potent than vinblastine toxic by itself. must be conjugated to an antibody
47
Major issues for T cell-based immunotherapy
- central tolerance: repertoire to self is irrevocably compromised - immunosuppression/peripheral tolerance
48
Interleukin-2 is a
recombinant protein multiple immunologic effects highly pro-inflammatory cytokine extremely nonspecific
49
CTLA-4 and PD1 act as
brakes or checkpoints in the immune system
50
Blocking CTLA-4 and PD1 with antibodies
keeps T-cells activated
51
Ipilimumab binds to
CTLA-4 receptor and reverses the CTL inhibition
52
Ipilimumab indication
tx of advanced metastatic melanoma may require high-dose corticosteroids
53
Pembrolizumab, Nivolumab, Cemiplimab all bind
the program death-1 (PD-1) receptor and blocks its interaction with PD-Ligand 1 and 2 (PD-L1 and PD-L2)
54
Where is PD-1 expressed?
T-cells
55
Blocking PD-1
prevents inhibitory signaling within T-cells leading to enhanced tumor cell killing
56
Pembrolizumab, Nivolumab, Cemiplimab indication
advanced metastatic melanoma following tx w/ Ipilimumab and (if BRAF V600 mutation positive) a BRAF inhibitor also approved for non-small cell lung cancer if the patients tumor biopsy tests positive for PD-L1
57
Atezolizumab, Avelumab, Durvalumab bind
PD-L1 receptor and block interaction with PD-1
58
Where is PD-L1 expressed
macrophages and tumor cells
59
Atezolizumab, Avelumab, Durvalumab indication
NSCLC in patients w/ EGFR or ALK mutations that have progressed on those therapies
60
Sorafenib is a
multi-target kinase inhibitor hits RAF, VEGFR, PDGFR
61
Sorafenib indication
unresectable liver cancer
62
anti-tumor immunity can be enhanced by
preceding it w/ radiation
63
radiation produces
neo-antigens
64
How do Bi-specific T-cell Engagers (BiTE) work?
- act independently of specificity of T-cell receptor (TCR) - allow T-cells recognition of tumor-associated surface antigen (TAA) - Do not require MHC Class I and/or peptide antigen
65
Blinatumomab binds to
CD19 and CD3 physically brings an activated T-cell into proximity with the tumor cell activated T-cell will then lyse the tumor cell
66
Blinatumomab indication
B-cell lymphomas DON'T CONFUSE THESE WITH CHIMERIC ANTIBODIES
67
What does CARs stand for?
Chimeric Antigen Receptor
68
What is CAR T-cell Therapy
- remove blood from pt to get T-cells - Make CAR T cells in the lab - Grow millions of CAR T cells - Infuse CAR T cells into pt - CAR T cells bind to cancer cells and kill them
69
``` Tisagenlecleucel (Kymriah) Brexucabtagene autoleucel (Tecartus) Axicabtagene Ciloleucel (Yescarta) Lisocabtagene maraleucel (Breyanzi) ``` are examples of
CAR T-cell therapy pt is essentially immunized against CD-19 All immature B-cells are eliminated The T-cells live on indefinitely
70
The future of T-cell therapy
the best success has been in B-cell leukemia's in which the CAR is specific for CD19 adopting this same approach into other tumor types has been a challenge due to toxicity Need a way to turn the CAR T-cells off
71
Sipuleucel-T approved for
metastatic prostate cancer
72
Sipulcel-T is a
“Drug” is PAP-GM-CSF, a recombinant human protein containing prostatic acid phosphatase (PAP) linked to granulocyte macrophage colony stimulating factor (GM-CSF), an immune cell activator goal = stimulate a pt's own immune system to attack the cancer
73
Sipulcel-T indicated for
tx of minimally symptomatic metastatic hormone-refractory prostate cancer
74
Hepatitis B Virus (HBV) associated w/
liver cancer
75
HPV Vaccines
Human Papilloma Virus (HPV) can act as a primer for cancer development -HPV is a DNA virus that produces proteins (E6 and E7) that increase cell proliferation and allow for accumulation of DNA mutations. -HPV types 16 and 18 are the major causative agents for cervical cancer and therefore can be vaccinated against as means to prevent HPV infection and hence cervical cancer. - Also predicted to protect against vuvlar, vaginal, anal and penile cancers that are associated with HPV infection. Quadrivalent HPV (HPV4, Gardasil) Is made up of the major capsid protein L1 of HPV types 6, 11, 16, and 18 Bivalent HPV (HPV2, Cervarix) Is made up of the major capsid protein L1 of HPV types 16, and 18 Both administered in three doses over a period of 6 months.

Therapeutics IV (19 decks)

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