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Foundations 9 > Immunotherapy > Flashcards

Immunotherapy Flashcards

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1
Q

Surgery

A

Remove as much of bulk as possible

If benign, may not need follow up

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2
Q

Surgery cannot do anything for

A

Micro-metastatic disease

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3
Q

Radiation therapy

A

Disrupts DNA of proliferating cells and disrupts ability to make new DNA
Bone marrow, lining of gut, hair follicles might also be damaged
Destroys residual tumor in surgical field

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4
Q

Chemotherapy

A

Us of cytoreductive compounds to reduce tumor burden and destroy micro-metastatic tumor deposits
Can be used for both metastatic and micro-metastatic dz
Disrupts metabolic paths like cytoskeleton, etc.
Bone marrow particularly sensitivr

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5
Q

Limitations of conventional therapies

A

Resistance (like DNA repair mechanisms)

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6
Q

Solution for limitations of conventional therapies

A

Need less toxic therapies (maintain BM)
Need to address residual dz, mets, and micro-mets
Need to personalize
Need therapies where chemo lacking or unresectable

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7
Q

Immunotherapy

A

Biologic therapy
Specific
Good for micrometastatic
Some can have memory

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8
Q

Passive immunotherapy

A

Generate therapeutic reagenet large scale in labs

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9
Q

Active immunities

A

Inject antigen and let paitents immune system do work

Therapeutic vaccines

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10
Q

Cytokine administration

A

Can be toxic, have a short half life, can be combined

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11
Q

Renal cell cancer and melanoma

A

IL-2 and alpha IFN

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12
Q

CML and hairy cell leukemia

A

Alpha IFN

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13
Q

Too toxic cytokines

A

4,6,12, TNF

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14
Q

Currently being explored cytokines

A

7, 15

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15
Q

Is cytokine therapy durable?

A

No, about 4.1 months

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16
Q

-omab

A

Fully mouse, most immunogenic

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17
Q

-ximab

A

VR - mouse, CR - human…chimeric

Less immune response against Fc region

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18
Q

-zumab

A

Humanized

CDR-mouse…everything else human

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19
Q

-umab

A

Fully human…least immunoigenic

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20
Q

Things ABs can do

A

ADCC
CDC
Growht inhibition
Prevent metastasis
Monoclonal-AB toxin conjugate (like chemo or toxin)
Radiolabeled monoclonal AB (or radio-nuclide that kills_

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21
Q

Examples of ADCC

A

NK, macro, granulocytes

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22
Q

Infliximab used for

A

Rheumatoid arthritis

Against TNF

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23
Q

Nataliuizimab used for

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A

MS…reduced number of lesions

24
Q

Cellular nonspecific immunotherapies

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A

Macrophages, NK cells, LAK

25
Cellular specific immunotherapies
TILs
26
LAKs with pros and cons
IL-2 infusions with NK cells Need Leukapheresis Pros - worked for advanced, 25-30% response Cons - required ICU, expensive, not durable
27
TILs with pros and cons
T cells from solid tumor biopsies expanded in IL-2 Pros - autologous and personalized, de-bulked, evidence mounted that infusion with specific anti tumor specificity (MHC restricted) resulted in tumor regression Cons - sterility, equipment and staff, time to tx, expensive
28
TIL protocol
Resect lesions Enzyme digest Culture in IL-2 Reinfuse TIL with Il-2
29
GP100
Found in melanocytes...can be target
30
Tyrosinase
Melanocytes Expressed higher when dividing CD4 and CD8s have receptors for tyrosinase Need to break tolerance
31
Autologous T cell immunotherapy
Excise tumor and take T cells needed...select the MHC restricted ones and only proliferate those
32
Tx with fluberivine and cyclophosphamide
Decrease T cell counts...used with T cell immunotherapy to "make room" for new T cells
33
One advantage of TIL
Can tailor it to act just on tumor cells
34
Other cellular immunotherapies
Make tumor cells act as APCs Modify antigen spceificity of T cells - isolate specific TCR clone, and put back in (PBMC) CART cells - AB variable regions attached to T cell signaling domains to recognize a single tumor antigen
35
Genetic mods of tumor cells
Insert therapeutic gene to enhance response Insert costimulator gene Insert cytokine gene
36
CART cells effectively
Bypass the T cell specificty and allow AB binding region to activate T cell...only works against B cell tumors
37
What is critical for T cell memory?
IL-7 receptors on T cells
38
Splicing of memory and naive T cells
Memory/effector - excludes A,B, C exons (CD45RO) | Naive - includes A,B, C exons (CD45RA)
39
Types of memory T cells
Central, effector, resident
40
B cells primary
M, G, A, E...low affinity and hypermutation
41
B cells secondary
G, A, E | high affinity and hypermutation
42
MART
Melanoma antigen recognized by T cells
43
Vaccine requirement for cancer
Must be inactivated
44
Inactivation process
Infect human cultured cells, transfect monkey cells, take back out and then inject into humns
45
Adjuvants
Alum - aluminum hydroxide/ohosphate formulations
46
Depot effect of adjuvants
Concentrate antigen in one place os it does not dilute out too quikcly
47
Bystander effect of adjuvants
Induce cytokine release...due to immune response to adjuvant
48
How does alum work?
Stimulates clusters of proteins called inflammasomes inside certain cells...release cytokines Operate in parallel with TLRs
49
Admin of vaccines
Inoculation - most feared but most common Ingestion - preferred Nasal prep- occassional
50
Provenge vaccine
Against prostate cancer Induces equilibrium (4.1 months) Isolate CD14 positive monocytes and culture to make dendritic cells...pulse cells to prostate attached to GM-CSF...this signals BM to release granulocytes and monocytes and increase APC precursors Downside is that MDSCs are also released which are suppressive
51
Autologous dendritic cell vaccine
Non-resectable non small cell lung cancer Autologous CD14+ derived DCs Used GM-CSF
52
ELISPOT analysis for
Gamma-IFN...key in anti-tumor response
53
IL-6, IL-10, and IFN-gamma importance
IL-6 higher in non-responders (inflammatory) IL-10 - higher in some non-responders (Th2) IFN-gamma - important for anti-tumor
54
Cytokine levels with stage in disease
Th1 wont change | Th2 will increase with stage
55
Checkpoint inhibitors
CD80/86;CTLA4 (ipilimumab/Yervoy) | PD1:PDL1
56
Mech of CTLA4 checkpoint inibitor
Use AB for CTLA4 which prevents inhibition of T cell and therefore allows it to live...induces equilibirium (14.8 months)...works only in lymph node between dendritic and T cell
57
Mech of PD1:PDL1 inhibitor
PDL1/PD1 AB works on T cell (PD1) or cancer cell/dendritic cell with PDL1...cancer cells can express this sometimes Used in lymph node AND at tumor site

Foundations 9 (6 decks)

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