Therapeutic Cytokines Flashcards

1
Q

Define Monoclonal Antibodies

A

Immunoglobulin designed to target oncoproteins expressed by tumor cells and to cause an immune response that destroys cancer cells (Targeted Therapy).

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2
Q

Define Adoptive T Cell Transfer

A

A treatment using host T cells to boost the natural ability of immune activity to fight cancer. T cells are isolated from the patient tumors and grown into large batches in the lab. These T cells are then infused into the patient body.

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3
Q

Define Immunoregulatory Cytokines

A

Multiple functional proteins playing important roles in body’s immune responses and having the immune-regulatory ability to control cancer cell growth. The two main types of cytokines used to treat cancer are interferons and interleukins.

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4
Q

Define Treatment Vaccines

A

Antigen-presenting cells (APC) with PAP/GM-CSF as the vaccine active component to stimulate immune response against cancer

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5
Q

Define BCG

A

An immune-stimulus used to treat bladder cancer. When inserted directly into the bladder with a catheter, BCG causes an immune response against cancer cells.

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6
Q

Define Interferons

A

Cytokine produced by the cells of the immune system (T/B cells)

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7
Q

Type 1 Interferon

A

IFN-α, IFN-β

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8
Q

Type II Inferferon

A

IFN-γ

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9
Q

Mechanisms of IFN-α activation

A

o Interferon activity NEEDS a receptor (without this, it is useless)
o When the receptor is bound, it will dimerize and activate the JACK pathway which activates additional intracellular proteins STAT1/2
 STAT1/2 activates many genes in the nucleus → protein expression and increased cell cytotoxicity or apoptosis

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10
Q

Potential MOA of IFN in Tumor Therapy

A

o Direct inhibition of cancer cell proliferation.
o Enhancement of cytotoxic T cell activities that kill cancer cells. (MOST IMPORTANT)
o Cell cycle regulation leading to tumor cells cytostasis and apoptosis.

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11
Q

Pharmacokinetics of IFN

A

Half-life is very short (2-3 hours)

If a person’s kidneys are normal and good, then you should not find any interferon in the urine

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12
Q

IFN Indications

A
o	Ph+ CML
o	Hairy cell leukemia
o	Follicular lymphoma
o	AIDS-related Kaposi’s sarcoma
o	Malignant melanoma
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13
Q

IFN Acute AE

A

Flu-like: fever, headache, chills

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14
Q

IFN Chronic AE

A

Depression and suicidality
Fatigue and weakness
Incomplete Reiter’s Syndrome (deep ulcers on the tongue)

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15
Q

***Do NOT use IFN-α if:

A

o Pregnant or breast feeding
o Allergic
o Autoimmune hepatitis (positive anti-nuclear antibody-Your body produces its own liver antibody so that your body attacks your own liver)
o Newborn or premature infants

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16
Q

IL-2 Molecular Mechanisms

A

 IL-2 activity requires its binding to IL-2 receptor.
 IL-2 receptor belongs to class I cytokine receptor family
 IL-2 receptor is composed of 3 subunits (IL-2Rα, IL2Rβ, and γc.
 Signaling is transmitted by members of the JAK, and STAT family.
• Activates or produces cytokines

17
Q

IL-2 Drug Mechanism

A

 Enhancing lymphocyte cytotoxicity (aka cancer cell killing)
 Inducing lymphokine-activated (LAK) and natural (NK)) activity (aka enhanced killing activity
 Inducing TNF-alpha, IFN-gamma production (inflammatory cytokines)
 Mainly: stimulates T-cell proliferation (rapid replication)

18
Q

IL-2 PK

A

Even shorter half-life than IFN (15-85 minutes)
Leaks into tissue upon injection
DO NOT vigorously shake because the proteins will degrade

19
Q

IL-2 Indication

A

 Adults Metastatic Renal Cell Carcinoma

 Adults with Metastatic Melanoma

20
Q

***IL-2 Clinical Condition Requirements

A

Normal cardiac and pulmonary test via thallium stress test

21
Q

IL-2 Drug interaction

A

Nephrotoxic, myelotoxic, cardiotoxic, hepatoxic drugs

Glucocrticoids reduce side effects but also reduce antitumor effects

22
Q

IL-2 Precautions

A

Normal cardiac and pulmonary function
Impaired neutrophils so increased risk of infection
Capillary leak syndrome

23
Q

Define Capillary Leak Syndrome

A

Leak into the tissues with body fluid leading to edema; if this happens in the lungs, you cannot breath; if this happens in the heart, you die

24
Q

IL-2 AE

A
	HypOtension
	Pulmonary congestion
	Anemia
	Thrombocytopenia
	Capillary leak syndrome (pretty much leads to all the other AEs)