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Drug Delivery 2 > Immunotherapy 2 > Flashcards

Immunotherapy 2 Flashcards

1
Q

Dendritic cell

A

Release cytotoxic cytokines
Antigen presentation to T cells
In cancer:
Suppress T cell functions
Promote tumor growth and progression

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2
Q

T cell

A

Directly lyse cancer cells
Release cytotoxic cytokines
In cancer:
Release tumor promoting cytokines

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3
Q

Treg

A

Restore homeostasis to reduce chronic inflammation
In cancer:
Suppress anti cancer immune responses
Stimulate inflammatory cytokine production

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4
Q

Macrophage

A

Release cytotoxic cytokines
Antigen presentation to T cells
In cancer:
Promote angiogenesis, tumor proliferation, chemotaxis, invasiveness, and metastassi

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5
Q

Myeloid derived depressor cell

A

Limited
In cancer:
Suppress T cell functions
Recruit immunosuppressive immune cells

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6
Q

NK cell

A

Release cytotoxic cytokines
Directly cytotoxic to cancer cells
In cancer:
Limited

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7
Q

Cancer immunoediting

A

Elimination
Equilibrium
Escape

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8
Q

Elimination

A

Immunity works to destroy developing tumors long before they become clinically apparent
Immunosurveillance

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9
Q

Equilibrium

A

The process by which the immune system iteratively selects and/or promotes the generation of tumor cell variants with increasing capacities to survive immune attack

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10
Q

Escape

A

The immunologically sculpted tumor expands in an uncontrolled manner in the immunocompetent host

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11
Q

Why cancer immunotherapy

A

Improved overall survival as a result of combination with immunotherapy

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12
Q

Immunotherapeutics

A

Ideally can have prolonged and sustained protection by forming memory

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13
Q

Dogma of Immuno-Oncology

A

Release of cancer cell antigens
Cancer antigen presentation
Priming and activation
Trafficking of T cells to tumors
infiltration of T cells into tumors
Recognition of cancer cells by T cells
Killing of cancer cells

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14
Q

Types of cancer immunotherapy

A

Cytokines
Vaccines
CAR-T cells
Checkpoint inhibitors
Molecular agonists

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15
Q

Cytokines

A

Can directly influence the survival, activation, proliferation and differentiation of T cells as well as indirectly affecting these processes through effects on dendritic cells, macrophages and regulatory T-cells

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16
Q

Types and functions of cytokines

A

Mediates intracellular signaling to regulate homeostatsis of immune system
Has the ability to act on many different cell types to mediate diverse effects
Multiple have the same functional effects

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17
Q

Clinical applications of cytokines

A

IFNa: approved by FDA for adjuvant treatment of resected high risk melanoma patients and several refractory malignancies
High dose IL-2: FDA approved for treatment of metastatic renal cell cancer and melanoma
Very limited clinical utility

18
Q

Cytokine SE

A

Hypotension, capillary leak syndrome, bleeding problems

19
Q

Cancer vaccines

A

Response modifiers working by stimulating or restoring the ability of immune system to fight cancer
Consists of preventative and therapeutic vaccines

20
Q

Tumor antigen vaccine classes

A

Tumor associated antigens
Tumor specific antigens

21
Q

Tumor associated antigens

A

Over-expressed proteins, differentiation antigens
—variable specificity, high tolerance, high prevalence in multiple patients
Cancers testis antigens
—good specificity, low tolerance, high prevalence in multiple patients

22
Q

Tumor specific antigens

A

Oncoviral antigens
Shared neoantigens
Private neoantigens
—ideal specificity, no tolerance, high prevalence in multiple patients (low prevalence in private neoantigens)

23
Q

Clinical applications of preventative cancer vaccines

A

Preventative:
-HPV for cervical cancer and head and neck cancer
-HBV for liver cancer caused by hepatitis B virus
Therapeutic
-Sipluleucel-T: for metastatic hormone-refractory prostate cancer
-Most probably be used in the adjuvant or neoadjuvant setting for the treatment of patients with minimal residual disease or more indolent metastatic disease, or those with a high risk of recurrence.

24
Q

MABs for triggering the immune system

A

Antibody-dependent cell-mediated cytotoxicity (ADCC)
Attach themselves to cancer cells, making it easier for the immune system to find them

25
Q

Examples of MABs for triggering the immune system

A

Rituximab
Cetuximab
Trastuzimab

26
Q

MABs for inhibiting immune checkpoints

A

Checkpoint inhibitors block proteins that stop the immune systems attacking cancer cells

27
Q

MABs for inhibiting immune checkpoints

A

Ipilimumab
Atezolizumab
Pembrolizumab

28
Q

CD28

A

Interacts with CD80 or CD86 which are upregulated on activated antigen presenting cells
Amplifies TCR signaling to activate T-cells

29
Q

CTLA-4

A

Interact with CD80 or CD86
Dampens the expression of T-cells by sending inhibitory signals to it

30
Q

Anti-CTLA-4

A

Promotes T cell priming by APCs in lymph nodes

31
Q

Tregs and CTLA-4

A

Treg constitutively expresses CTLA-4
Anti-CTLA-4 functions partially due to depleting and suppressing Tregs

32
Q

PD-1/PD-L1

A

Induced by TCR/CD28-mediated activation signaling
PD-L1: expressed in infected cells and tumor cells as well as antigen presenting cells
PD-L2: generally expressed in antigen presenting cells

33
Q

CTLA-4 vs. PD-1 in T cells

A

CTLA-4 is an on off switch
PD-1 is dynamic, milder response to blocking

34
Q

PD-1/PD-L1 mechanism

A

Inhibits T-lymphocyte proliferation, survival and effector functions inducing apoptosis of tumor specific T-cells

35
Q

Anti PD-1

A

Promote effector functions in T cells
Rescue T cells from adaptive resistance

36
Q

Anti-PD-1 v. Anti PD-L1

A

In principle may work differently due to diverse ligand-receptor interactions
In practice, they shoe similar response levels of efficacy and cytotoxicity

37
Q

Combined Immune Checkpoint Blockade

A

Improved efficacy by combining anti-CTLA-4 and anti PD-1
Increased toxicity by the combination

38
Q

TIL therapy

A

Tumor infiltrated lymphocyte
Tumor resection
Isolation of TIL and initial outgrowth ex vivo
Rapid expansion of TIL
Returned to patient

39
Q

Adoptive cell transfer (ACT)

A

Giving prepared T cells to the patient

40
Q

T cell receptor therapy

A

Isolation of peripheral T cells via leukapheresis
Introduction of a retrovirus
Transduction of viral vector
(CAR therapy)
Specific TCR
ACT

41
Q

Specific TCR types

A

Melanoma differentiation antigen recognition
Overexpressed antigen recognition
C/T antigen recognition
Viral antigen recognition

42
Q

Chimeric antigen receptor (CAR) therapy

A

1st gen: extracellular, transmembrane and Intracellular activating domain
2nd gen: 1 customatory domain often CD28 or 4-1BB
3rd gen: 2 customatory domains (CD28+4-1BB or OX-40)
4th gen: CAR “truck” NFAT, Inducible cytokine

Drug Delivery 2 (8 decks)

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