Block 3 Lecture 3 -- Vaccines and Immunotherapy Flashcards

1
Q

How do CTLs kill?

A

1) granzyme and perforin

2) FasL/Fas

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2
Q

Where is FasL and where is its ligand?

A

FasL located on CTL

Fas = CD95 on tumor

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3
Q

What are the results of FasL/Fas binding?

A

caspase activation

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4
Q

What is required for both methods of CTL killing?

A

CD8/TCR + pMHC-I

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5
Q

What are ways to evade the immune response?

A

1) low immunogenicity
2) tumor treated as self-antigen
3) antigenic modulation
4) tumor-induced immune suppression
5) tumor-induced privileged site
6) immuno-editing

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6
Q

What is an adjuvant?

A

substance added to or emulsified with antigen capable of increasing Ab or T cell production to the antigen

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7
Q

What are the requirements for an antigen used in a vaccine?

A

1) able to induce clonal B/T cell differentiation and proliferation
2) induce memory response

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8
Q

What adjuvant is approved in the US?

A

alum (aluminum hydroxide/phosphate) formulations

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9
Q

How does alum as an adjuvant work?

A

1) depot to trap antigen at injection site
2) continued stimulation of immune system (more APCs recruited)
- - other adjuvants may direct pMHC presentation

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10
Q

When are adjuvants usually used?

A

for toxin-vaccines

– bacterial/viral components may not need adjuvant

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11
Q

What is Provenge?

A

autologous cellular immunotherapy

– DCs loaded with Ag ready to activate T cells

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12
Q

When is Provenge due?

A

for asymptomatic or minimally asymptomatic metastatic castrate-resistant prostate cancer

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13
Q

What are the 3 functions of mAbs in cancer?

A

1) can target immune system to destroy tumor cells
2) can inhibit cell signaling/proliferation
3) can carry conjugated drugs/radiolabel

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14
Q

What are the advantages of cancer immunotherapy?

A

1) durable response
2) slows tumor growth
3) relatively non-toxic

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15
Q

What are the disadvantages of cancer immunotherapy?

A

1) low response rate
2) altered pattern of response (delayed)
3) autoimmune-related adverse effects

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16
Q

What are the 2 main interactions in the immunosynapse?

A

1) pMHC + TCR

2) B7 (APC) + CD28

17
Q

How can the pMHC + TCR synapse be improved?

A

1) vaccines
2) stimulation of DCs with antigens
- - provenge

18
Q

How can the B7 / CD28 interaction be improved?

A

1) increased B7-1/2 expression
- - modified cell lines (drug delivery is a problem)
2) blocking CTLA4
- - ipilimumab
- - tremulimumab

19
Q

What other signal is important in the immune synapse?

A

PDL1 (APC/tumor) - PD1

– PD1 is inducible, expressed on tired T cells

20
Q

What is the PD1 inhibitor?

A

Nivolumab

21
Q

What is the function of IL-2?

A

immune cell growth and division

22
Q

How are cancer immunotherapies characterized?

A

1) non-specific vs. specific

2) passive vs. active

23
Q

What does CAR-T stand for?

A

chimeric antigen receptor T cell therapy

24
Q

How are CAR-T cells made?

A

1) T cells removed
2) modified with virus to tumor-specific receptor composed of multiple fragments
3) population expanded in vitro

25
Q

What is the goal of CAR-T cell therapy?

A

1) want CAR-T cells to recognize Ag

2) want CAR-T cels to expand in vitro

26
Q

What are examples of non-specific immunotherapy?

A

1) CAR-T
2) cytokines
3) mAbs