1
Q
what 2 things characterize cancer
A
- accumulation of genetic alterations
- loss of normal cellular regulatory processes
2
Q
what is 1 consequence of cancer (cellular)
A
expression of different antigens
3
Q
what does cancer lead to (cellularly)
A
presentation of peptides bound to MHC 1 molecules on surface of cancer cells
4
Q
what is a way that you can distinguish normal cells and cancer cells
A
presentation of peptides bound to MHC 1 molecules on surface of cancer cells
5
Q
what are 3 types of tumor antigens
A
- mutational antigens (neoantigens)
- tumor associated antigens
- cancer/testis antigens
6
Q
what is special about mutational antigens (neoantigens)
A
they are completely absent from normal host cells
7
Q
what are mutational antigens (neoantigens) derived from
A
mutated self-proteins or oncogenic viral proteins
8
Q
are there mutational antigens (neoantigens) in normal cells
A
no
9
Q
are there tumor associated antigens in normal cells
A
very low levels
10
Q
what are tumor associated antigens
A
nonmutated proteins overexpressed in cancer cells
11
Q
what do tumor associated antigens result from
A
genetic amplification
12
Q
are there cancer/testis antigens in normal cells
A
only in reproductive tissues
13
Q
do all tumors express cancer/testis antigens
A
no only by various tumor types
14
Q
what happens after cancer releases antigens
A
cancer antigen presentation by APCs
15
Q
what causes cancer to release antigens
A
often cell death
16
Q
what happens once cancer antigens are presented by APCs
A
it causes T cells to rush to the tumor and infiltrate
17
Q
what happens once T cells recognize cancer ells
A
they kill them
18
Q
what must occur at the same time as tumor antigen presenting
A
cytokine release
19
Q
what are 3 examples of cancer-immune cycle not working
A
- tumor antigens may not be detected
- T and DCs cells may not treat antigens as foreign
- T cells may not get to and into the tumors
20
Q
what is the role of cancer microenvironment
A
suppresses effector T cells
21
Q
what is the main goal of cancer immunotherapy
A
initiate or reinitiate a self sustaining cycle of cancer immunity
22
Q
what may be a downside of cancer immunotherapy
A
unwanted damage to normal cells and tissues, autoimmune
23
Q
what are 3 sites for therapeutic intervention
A
- promoting antigen presentation functions of DC
- promote protective T cell responses
- overcoming immunosuppression in the tumor
24
Q
how do you promoting antigen presentation functions of DC (1 word)
A
vaccines
25
how do you promote protective T cell responses
engineering T cells (CAR T cells)
26
how do you overcoming immunosuppression in the tumor
checkpoint blockers
27
what is vaccination
administration of an antigen to produce immunity to a disease
28
what is cancer vaccines
formulation of TAs able to elicit an immune response to arrest the progression of cancer and prevent it from recurring
29
what do cancer vaccines induce
specific and long lasting lasting immune response against TA
30
what do classical vaccines rely on
random encounter of the vaccine with host DCs
31
what are DNA vaccines
naked DNA plasmids designed to deliver genes encoding tumor antigens
32
how are the DNA plasmids engineered in DNA vaccines
to include genes coding for co stimulatory molecules (Cyokines)
33
what happens to the antigen encoded by DNA vaccine
it is expressed and presented on MHC molecules
34
which MHC molecules are antigens presented on with DNA vaccines
both 1 and 2
35
which T cells are activated with DNA vaccines
CD4 and CD8 t cells
36
do DNA vaccines activate innate immunity
yes
37
what do they inject with cell based tumor cell vaccines (older ones)
whole tumor cells or cell lysates of allogenic source
38
what do they inject with cell based tumor cell vaccines (newer ones)
autologous tumor material
39
what are tumor cells co injected with in cell based tumor cell vaccines + why
adjuvant and/or cytokines or growth factors to increase immunogenicity
40
how are tumor cells engineered in cell based tumor cell vaccines
to express immunostimulatory cytokines or co-stimulatory molecules
41
what do they culture from blood in DC vaccines
monocytes
42
what do they load immature DCs with in DC vaccines + why
with antigens so they mature
43
what do they do to the monocytes they extract from blood in DC vaccines
they are cultured with various cytokines to produce immature DCs
44
what do they reinfuse back into the patient in DC vaccines
mature DCs
45
what do DC vaccines induce in the human
antigen specific T and B cell responses
46
where do they induce DC activation in DC vaccines
ex vivo
47
what type of vaccine is DC vaccine
cell based
48
what are the 2 types of cell based vaccines
tumor cell vaccines and DC vaccines
49
what do they use in protein/peptide based vaccines
identified tumor antigens
50
what are 3 types of tumor antigens used in protein based vaccines
- whole TA (protein)
- TA-derived peptides
- synthetic peptides containing the neoantigen sequences
51
what are antigens injected with in protein vaccines
adjuvant (boost immune ersponse)
52
what happens to protein vaccines once they are in the body
captured by tissue resident DCs, presented with MHC 2 (maybe 1 too)
53
how do recombinant viruses as vaccines work
the viruses are engineered to express a defined TA
54
what are major advantages to recombinant viruses as vaccines work
strong immunogenicity which leads to significantly greater immune response
55
what are major obstacles to recombinant viruses as vaccines work
presence of development of neutralizing antibodies against viral proteins
56
what is special about oncolytic viruses
they only replicate in cancer cells, not in normal cells
57
what do oncolytic viruses promote
anti tumor responses
58
what is the 2 ways that oncolytic viruses can be used
in situ (inside the tumor) and systemic
59
what does infection with oncolytic viruses cause
release of TAs and PAMPs and DAMPs
60
how do oncolytic viruses kill cells
they enter cells, cause the release of TAs and PAMPs and DAMPs which then start the immune response
61
how do personalized vaccines work (3 steps)
Take tumor sample from patient, do analysis of transcript, detect neoantigens/ tumor antigens that may be efficient to activate the immune system
62
what are 2 T cell receptor targets used for cancer immunotherapy
TCR and CAR (chimeric antigen receptor)
63
where do the TCRs come from for T cell cancer immunotherapy
responding patients
64
where do the CARs come from for T cell cancer immunotherapy
synthesized from molecular biology techniques
65
what is involved in T cell cancer immunotherapy with the TCR and CAR
insertion into T cells the receptors that can detect tumor antigens
66
what are CAR T cells
T cells that express CARs
67
what do CAR T cells recognize
tumor antigen directly on the surface of a tumor independently of MHC
68
do CAR T cells use the MHC
no
69
what is the structure difference of endogenous and engineered TCR
very similar
70
what is the structure difference of endogenous and engineered CARs
they lack TCR chains
71
what are the 2 things that make up CAR
antibody derived antigen recognition domain (extracellular, VL and VH) and intracellular T signalling stimulation domain
72
what does the intracellular T signalling stimulation domain of CAR do
recruits endogenous downstream signalling molecules
73
what do CAR T cells do (general + 3 specific)
provide tumor specific effector cells with enhanced functionality (superior cytotoxicity, persistence, antigen recognition)
74
what does the antibody derived antigen recognition domain do
recognizes cancer cells
75
how do they get the antibodies for CAR
from the same patient
76
where do "off the shelf" allogenic CAR T cells come from
healthy donors then recombinant DNA
77
what is the role of co inhibitory immune checkpoints
prevent aberrant or chronic activation of the immune system
78
how do cancer cells use the co inhibitory immune checkpoints
- to damped anti-tumor T cell responses
| - promote tumor immune escape
79
what do checkpoint blockage therapies do to the immune system (which phases)
reactivate induction and effector phases of anti-tumor T cell responses
80
what happens with CTLA4 checkpoint blockade
supports the induction phase of anti-tumor T cell responses
81
what happens with PD1 checkpoint blockade
maintains the effector phase of anti tumor T cell responses
82
what is ipilimumab
fully human mAb against CTLA4
83
what is the mechanism of ipilimumab
blocks interaction of CTLA4 with CD80 86 during antigen presentation in lymph nodes
84
what is the result of ipilimumab
promotes T cell production and disinhibits T cell response expansion
85
what % of human cancer express PD-L1
20-50%
86
what can upregulate PDL1 expression on tumor cells
constitutive oncogenic signalling
87
what are 2 drugs that treat the PD cycle
Nivolumab and Atezolizumab
88
what is Atezolizumab
Fully humanized mAb against PDL-1
89
what is Nivolumab
Fully humanized Ab against PD-1
90
what are 2 things that Atezolizumab cause
- reduce immunosuppressive signals in tumor microenvironment
| - increase T cell mediates immunity against tumor
PMCOL 344
flashcards
Decks in class (27)
# Cards
-
GI 1 - intro64
-
GI 2 - acid143
-
GI - emesis53
-
GI - diarrhea95
-
GI - laxatives74
-
GI - Crohn's and Colitis51
-
1-metabolism29
-
Plasma Lipids88
-
Statins63
-
Other lipid drugs84
-
Obesity Intro117
-
Obesity treatments32
-
Diabetes-149
-
Diabetes-285
-
diabetes-395
-
Anti-Platelets97
-
Anti-Coagulants78
-
Hematopoietic System-Iron63
-
Hematopoietic System-B12 and Folate78
-
Immune-1109
-
Immune-281
-
Immune-3104
-
Immune-466
-
Immune-587
-
Immune-669
-
Immune-784
-
Immune-890
