Immunotherapies Flashcards
(112 cards)
1
Q
are biologics structure known or unknown
A
unknown
2
Q
are biologics more or less susceptible to physical conditions
A
more susceptible
3
Q
do biologics have more or less potential for immune reaction
A
more potential
4
Q
how are biologics approved
A
351(a) Biologic License Application
5
Q
meaning of the 4 letter suffix of biologics
A
no meaning. used to identify/distinguish
6
Q
database of biological products
A
Purple Book
7
Q
who MANAGES the Purple Book
A
FDA
8
Q
who REGULATES the Purple Book
A
CDER and CBER
Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research
9
Q
MOST therapeutic mAb are
A
IgG1
10
Q
an antibody produced by a single clone of cells or cell line consisting of identical antibody molecules
A
monoclonal antibody
11
Q
monoclonal antibodies have ______ specific for target and are designed to act with ______ molecules
A
high specificity, one molecule
12
Q
2 processes to produce mAb
A
hybridoma, recombinant
13
Q
which IgG does NOT have immune effector functions (ADCC/CDC)
A
IgG4
14
Q
each IgG subclass contains a different _____ chain
A
heavy chain
15
Q
more murine —-> ________ immunogenicity
A
increased
16
Q
potential for patient to develop anti-drug antibodies (ADAs)
A
immunogencity
17
Q
what type of Ig can ADAs be
A
IgG, IgM, IgE, IgA
18
Q
why does immunogenicity matter
A
adverse reaction, decrease efficacy
19
Q
pt develops IgE against drug, IgE activates mast cells/basophils
A
hypersensitivity
20
Q
in hypersensitivity pt develops _____ against drug
A
IgE
21
Q
does degree of humanization predict risk of infusion related rxns/hypersensitivty
A
NO
22
Q
are infusion related reactions immune mediated
A
No, can rechallenge pt
23
Q
are hypersensitivity reactions immune mediated
A
yes, must change drug
24
Q
can IRRs and hypersensitivity rxns still occur with fully human mAb
A
Yes
25
-omab
mouse (murine)
26
-ximab
chimeric
27
-zumab
humanized
28
-umab
fully human
29
route of mAb
parenteral
30
half life of mAb
days-weeks
31
elimination of mAb
reticuloendothelial macrophages
32
can mAb be used in combination with eachother
yes
33
3 types of antibody based therapies
unconjugated, conjugated, -pretargeted antibody conjugates
34
majority of mAb are _______ IgG
uncojugated
35
when mAb delivers a "payload" to a specific site
conjugated mAb
36
2 immune effector functions
Antibody-dep cellular cytotoxicity (ADCC)
| Complement-dep cytotoxicity (CDC)
37
immune effector functions are related to ____ region of mAb
Fc region
38
mAb binds target ---> Fc portion recruits immune cells to induce cytotoxicity
ADCC
39
mAb binds targer ---> Fc portion activates complement cascade
CDC
40
activation of complement may _____ ADCC
enhance
41
4 MOAs of mAb
ADCC, CDC, Alt signal transduction, Immunoconjugates
42
how do mAb alter signal transduction
binds to receptor or binds to ligand
43
glycosylation occurs at ____ domain of the _______ region
CH2 domain of constant region
44
what does glycosylation effect
PK properties and ability to induce ADCC and CDC
45
Fucose impacts ______ activity
ADCC
46
defucosylation leads to ______ ADCC
increased
47
Galactose impacts ____ activities
CDC
48
Mannose and Sialic acid impacts _____
Pharmacokinetics
49
variable domain + first constant region of each heavy and light chain
Fab Fragments
50
light chain + heavy chain variable region joined by a linker peptide
single chain variable fragment
51
light chain variable region OR heavy chain variable region
single domain antibody
52
2 immunoglobin chains of differing specificity are fused into a single antibody
bispecific/bifunctional antibody
53
Fc portion of an IgG is bound to something else
IgG1 fusion proteins (Fc fusion proteins)
54
key toxicity of anti-HER2 agents
heart failure
55
what type of antibody is Trastuzumab (Herceptin)
humanized IgG1
56
target of Trastuzumab (Herceptin)
HER2 receptor
57
MOA of Trastuzumab (Herceptin)
inhibit dimerization of HER2, activates ADCC
58
what is Ado-trastuzumab Emtansine (Kadcyla)
antibody drug conjugate
59
what is Emtansine
microtubule inhibtor
60
why does Emtansine have to be linked to trastuzumab
too toxic to give alone
61
MOA of Trastuzumab (Herceptin)
inhibit dimerization of HER2, activates ADCC, release Emtansine
62
TNF
tumor necrosis factor
63
what produces TNF
macrophages and T cells
64
what does TNF do
inflammatory mediator
65
key toxicities of anti-TNF agents
infection, malignancy
66
what is Etanercept (Enbrel)
IgG1 fusion protein
| TNF rec fused to Fc protein of IgG1
67
MOA of Etanercept (Enbrel)
bind TNF and prevent it from binding to receptor
68
what is Certolizumab Pegol (Cimzia)
humanized Fab' fragment
69
MOA of Certolizumab Pegol (Cimzia)
bind TNFa and prevent it from binding receptor
70
what does pegylation of Certolizumab Pegol (Cimzia) do
increase half life, decrease immunogenicity
71
does Etanercept (Enbrel) or Certolizumab Pegol (Cimzia) have ADCC or CDC activity
```
Etanercept (Enbrel) has SOME
Certolizumab Pegol (Cimzia) does NOT (lacks Fc portion)
```
72
mAb that is an immunotoxin
Moxetumomab Pasudotox (Lumoxiti)
73
indication of Moxetumomab Pasudotox (Lumoxiti)
hairy cell leukemia (B cells which are CD22+)
74
what is Moxetumomab Pasudotox (Lumoxiti)
murine anti-CD22 antibody fragment
75
MOA of Moxetumomab Pasudotox (Lumoxiti)
binds CD22+ cells, drug is internalized and toxin released that inhibits protein synthesis and triggers apoptosis
76
half life of Moxetumomab Pasudotox (Lumoxiti)
1.4 hours
77
antibody with short half life
Moxetumomab Pasudotox (Lumoxiti)
78
mAb that is a Radioimmunoconjugate
Ibritumomab Tiuxetan (Zevalin Y-90)
79
what is Ibritumomab Tiuxetan (Zevalin Y-90)
murine anti-CD20 IgG1 mAb
80
indication of Ibritumomab Tiuxetan (Zevalin Y-90)
non-Hodgkin lymphoma (B cells that are CD20+)
81
how does Ibritumomab Tiuxetan (Zevalin Y-90) cause cellular damage
beta emission
82
which mAb is a bispecific antibody
Emicizumab (Hemlibra)
83
indication of Emicizumab (Hemlibra)
hemophilia A (factor VIII def)
84
what is Emicizumab (Hemlibra)
modified humanized IgG4
85
what does Emicizumab (Hemlibra) target
clotting factors IXa and X
86
what does Emicizumab (Hemlibra) mimic
clotting factor VIII
87
which mAb is an immune checkpoint inhibitor
Pembrolizumab (Keytruda)
88
what is Pembrolizumab (Keytruda)
humanized IgG4 antibody
89
what does Pembrolizumab (Keytruda) target
PD1
90
do immune checkpoint inhibitor have immune effector functions
NO
91
which IgG subtype is more likely to have immune effector functions
IgG1
92
which IgG subtype is least likely to induce immune effector functions
IgG4
93
what type of cellular immunotherapy is CAR T-cell therapy
autologous
94
what does CAR stand for
Chimeric Antigen Receptor
95
how does CAR-T cell therapy work
patients own T cells are genetically modified with a gene that encodes a CAR---> extracellular domain recognizes antigen and activates intracellular domain---> activates T cell
96
2 components of a CAR
extracellular antigen recognition domain and intracellular signaling domain
97
what is started 5 days before CAR T cell therapy
lymphodepeleting therapy
98
2 major toxicities of CAR-T cell therapy
cytokine release syndrome and neurotoxicity
99
how are CAR-T cell toxicities managed
steroids
100
what type of cellular immunotherapy is Sipuleucel-T (Provenge)
autologous
101
indication of Sipuleucel-T (Provenge)
metastatic prostate cancer
102
how does Sipuleucel-T (Provenge) work
pt own antigen presenting cells are engineered to target PAP (prostate acid phosphatase) in prostate cancer cells
103
what does Sipuleucel-T (Provenge) use
antigen presenting cells
104
what does CAR-T cell therapy use
T cells
105
biologic that is highly similar and has no clinically meaningful difference from an existing reference product
biosimilar
106
how are Biosimilars approved
351(k) Biologics License Application
107
can a pharmacist auto-substitute a biosimilar
NO (only if it is deemed interchangeable)
108
2 requirements for a biosimilar
highly similar, no clinically meaningful differences
109
what does "extrapolation" mean
a biosimilar may be approved for other indications of the reference product even if it has not been studied for them, as long as there is evidence it demonstrates bio similarity for at least 1 indication
110
what may be substituted WITHOUT involvement of prescriber
interchangeable
111
how many biosimilar have been given an interchangeable designation
only 1
112
requirements for interchangeable dsignation
expected to produce same clinical result, evaluation of risk of switching back and forth
