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
Examples of MABs for triggering the immune system
Rituximab Cetuximab Trastuzimab
26
MABs for inhibiting immune checkpoints
Checkpoint inhibitors block proteins that stop the immune systems attacking cancer cells
27
MABs for inhibiting immune checkpoints
Ipilimumab Atezolizumab Pembrolizumab
28
CD28
Interacts with CD80 or CD86 which are upregulated on activated antigen presenting cells Amplifies TCR signaling to activate T-cells
29
CTLA-4
Interact with CD80 or CD86 Dampens the expression of T-cells by sending inhibitory signals to it
30
Anti-CTLA-4
Promotes T cell priming by APCs in lymph nodes
31
Tregs and CTLA-4
Treg constitutively expresses CTLA-4 Anti-CTLA-4 functions partially due to depleting and suppressing Tregs
32
PD-1/PD-L1
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
CTLA-4 vs. PD-1 in T cells
CTLA-4 is an on off switch PD-1 is dynamic, milder response to blocking
34
PD-1/PD-L1 mechanism
Inhibits T-lymphocyte proliferation, survival and effector functions inducing apoptosis of tumor specific T-cells
35
Anti PD-1
Promote effector functions in T cells Rescue T cells from adaptive resistance
36
Anti-PD-1 v. Anti PD-L1
In principle may work differently due to diverse ligand-receptor interactions In practice, they shoe similar response levels of efficacy and cytotoxicity
37
Combined Immune Checkpoint Blockade
Improved efficacy by combining anti-CTLA-4 and anti PD-1 Increased toxicity by the combination
38
TIL therapy
Tumor infiltrated lymphocyte Tumor resection Isolation of TIL and initial outgrowth ex vivo Rapid expansion of TIL Returned to patient
39
Adoptive cell transfer (ACT)
Giving prepared T cells to the patient
40
T cell receptor therapy
Isolation of peripheral T cells via leukapheresis Introduction of a retrovirus Transduction of viral vector (CAR therapy) Specific TCR ACT
41
Specific TCR types
Melanoma differentiation antigen recognition Overexpressed antigen recognition C/T antigen recognition Viral antigen recognition
42
Chimeric antigen receptor (CAR) therapy
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