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Drug Delivery 2 > Immunotherapy > Flashcards

Immunotherapy Flashcards

1
Q

passive targeting

A

relying on leaky vasculature with a drug loaded NP

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2
Q

Innate immunity

A

basic resistance to disease an individual is born with
rapid protection against microbes
response in place before foreign antigen presents
same response regardless of antigen or previous exposure

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3
Q

adaptive immunity

A

protection develops more slowly (days)
developed only after exposure to an antigen
effective only against the specific antigen
memory response against recurring antigen

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4
Q

humoral immunity

A

antigen on bacteria interact with B cell
B-cell gives antigen to helper T cell and releases cytokines
antibodies form from both B cell and helper T cells

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5
Q

cell mediated immunity

A

antigen presenting immune cell interacts with inactive helper T cell
activated helper T cell triggers cytokine release
helper T cell becomes a cytotoxic T cell and destroys infected cell

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6
Q

checkpoints

A

lower a stop sign that cancer cells usually present to immune cells

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7
Q

checkpoint inhibitors

A

work by taking the brakes off the immune system

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8
Q

cytokines

A

stimulate growth/activity of immune cells
used in recombinant IFNa therapy
–interferons: induce maturation of immune cells
–interleukins: stimulate activity of CD4+ and CD8+ T cells
–granulocyte-macrophage colony-stimulating factors (GM-CSF) promote T cell homeostasis and support dendritic cell differentiation

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9
Q

cytokines in clinical application

A

used for lymphocyte promotion in various cancers

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10
Q

adoptive T cell transfer

A

isolate patient own T cells and in vitro engineer T cells
chimeric antigen receptor T cells: genetically engineered T cells specific for antigen on tumor cells
CD29 CAR-T cells first approved for B cell lymphoma treatment

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11
Q

adoptive T cell transfer challenges

A

cytokine storm/cytokine-release syndrome
tumor lysis syndrome
persistent normal B-cell aplasia

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12
Q

adoptive t cell transfer

A

binds the antigen
creates gene against protein marker
modifies genes
creates T cell copies with modified gene
attacks tumor cells

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13
Q

activated t cells from patient

A

t cell isolated form tumor
viral vector encoding tumor specific TCR
human t-cell engineered to express TCR
expand population in culture

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14
Q

genetically engineered activated t cell

A

clone chimeric receptor into retroviral vector
create human t-cell expressing chimeric antigen receptor

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15
Q

clone human MHC class 1 or 2 genes activated t-cells

A

immunize mouse with human antigens
isolate mouse human T cell
clone mouse TCR into retroviral vector
human T cell expressing mouse TCR

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16
Q

CART cells

A

MHC independent
100x more antigens required on target
t cell transduced with tumor specific CAR
CAR: single fusion molecule with antigen specificity plus signaling domain

17
Q

TCRT cells

A

MHC dependent
1 antigen required on target

18
Q

Three types of CAR

A

based on costimulatory signals

19
Q

advantages of CAR-T cells

A

live drug
tumor recognition independent of antigen presentation
multiple selection on antigen
design flexibility

20
Q

liquid tumors

A

leukemia, lymphoma
–mutation in hematopoietic progenitor cells
–B cells, T cells and myeloid cells
–chronic or acute leukemia
–recurrence due to residue cells in bone marrow

21
Q

CD19 CAR-T cells

A

CD19 is a cell surface protein whose expression is restricted to B cells and B cell precursors
It is not expressed on HSC
It is expressed by most B cell malignancies

22
Q

CAR-T cells for solid tumor treatment

A

produce immune suppressing agents such as checkpoint PD-L1
Difficult for CAR-T cells to infiltrate

23
Q

barriers in solid tumor

A

physical barrier
metabolic restriction
immunosuppressive microenvironment
immunosuppressive pathways

24
Q

physical barrier in solid tumor

A

extracellular matrix
abnormal tumor vasculature

25
Q

abnormal tumor vasculature

A

leaky, hypoxic, high interstitial fluid pressure prevents medication from reaching

26
Q

abnormal tumor vasculature

A

leaky, hypoxic, high interstitial fluid pressure prevents medication from reaching

27
Q

Immunosuppressive cells in solid tumor

A

MDSC, Th17, Treg, TAM

28
Q

MDSC

A

suppresses NK and T cells
–deplete essential metabolites
–produce ROS and RNS
–inhibition by direct contact
–inhibition by release soluble factors

29
Q

Treg cells

A

suppress T cells by
–inhibitory cytokines
–cytolysis
–metabolic disruption
–targeting dendritic cells

30
Q

TAMs

A

immunosuppressive, pro tumorigenic

31
Q

Immunosuppressive cell depletion

A

danger signals
tumor-derived antigens
chemotherapeutics
adjuvants
photothermal therapy
photodynamic therapy
radiotherapy
ultrasound

Drug Delivery 2 (8 decks)

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