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Cology 2 Exam 4 > Immune altering and Hormonal therapy - Slides 1-22 > Flashcards

Immune altering and Hormonal therapy - Slides 1-22 Flashcards

1
Q

How are tumor cells different than normal cells when it comes to our immune system?

A

Tumor cells express proteins on the cell surface, “Tumor associated cell surface antigens”
Cell surface antigens are susceptible to attack by patients immune system
Tumor cells are less antigenic than foreign cells

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2
Q

What is interferon alpha? How does it work?

A

An immunostimulant
Works by:
Increasing cytotoxicity of natural killer cells
Increasing phagocytic ability of macrophages
Increasing ability of macrophage to present “processed antigen” to T-helper cells

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3
Q

What types of Interferon alpha are they? How are they different?

A

Alpha 2A - Roferon-A - Lysine 23

Alpha 2B - Intron-A - Lysine 23

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4
Q

Indications for interferon alpha?

A 
Hairy cell leukemia
Kaposi's sarcoma
CML
Chronic Hep B
Malignant melanoma
Multiple sclerosis
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5
Q

How is Interferon alpha administered?

A

SubQ multiple times weekly up to 12 months

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6
Q

Adverse effects of Interferon alpha?

A

Flu-like symptoms (Fever, chills, myalgia, headache)
Hair loss
Diminishes with time with daily administration

Dizziness, confusion, depression, aggressive behavior, decreased mental status, visual problems, coma

Contraindicated in pregnancy, no breast feeding, passes to fetus

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7
Q

True or False: Interferon alpha is safe in pregnancy

A

False - can pass to fetus

No breast feeding either

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8
Q

What is Interferon B used for? What types are there?

A

Relapsing multiple sclerosis

Interferon B-1-a (166 aa)
Interferon B-1-b (165 aa)

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9
Q

What is interferon gamma? How does it work?

A

Interferon gamma-1b

Activates phagocytes, increases oxygen radicals

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10
Q

Indications for interferon gamma?

A

Prevents serious infections in chronic granulomateous disease (inherited immunodeficiency)

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11
Q

Toxicities for interferon gamma?

A

Flu like syndrome
GI distress
Weight loss
Depression

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12
Q

What is Aldesleukin?

A

It is an interleukin

Interleukins serve as molecular messengers between leukocytes

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13
Q

How many interleukins do humans have?

A

17

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14
Q

Aldesleukin MOA

A

IL-2 (Aldesleukin) acts as a T-cell growth factor
Stimulates proliferation and activation of lymphokine-activated killer cells (LAK) and tumor-infiltrating lymphocytes (TIL)

Turns on natural killer cells and induces interferon gamma

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15
Q

How is Aldesleukin administered?

A

IV or infusion for 5 day cycles with 5-9 days between cycles

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16
Q

Aldesleukin indications

A

Metastatic renal cell carcinoma
Metastatic melanoma
Colorectal cancer
Malignant lymphoma

17
Q

Adverse effects of Aldesleukin

A

Fever, chills, myalgia, nausea, vomiting
Capillary leak syndrome (87%) and hypotension (70% - requires pressor therapy)
Arrhythmias, MI, heart failure
CNS - headache, dizziness, mental changes, seizures, coma (73% CNS edema)
Hepatotoxicity
Myelosuppression

18
Q

Cautions with Aldesleukin

A

Extreme caution in patients with cardiac, pulmonary, renal, or hepatic disease or seizure disorders

Pregnancy and breast feeding should be avoided

Patients should understand serious adverse effects with normal therapeutic doses

19
Q

How do Immune Checkpoint Blockers work?

A

Immune checkpoints are points at which the immune system can be blunted to prevent overstimulation of the immune system
It contributes to the maintenance of immune tolerance to self-antigens

20
Q

What is CTLA-4?

A

Cytotoxic T-lymphocyte associated antigen-4, released by activated T-cells to dampen immune response

21
Q

What is PD-1?

A

Programmed cell death protein-1
Receptor that binds PD-L1 and PD-L2 ligands
Limits detrimental immune responses and limits autoimmunity, also thought to be released by tumor cells to give cells adaptive immune resistance

PD-1 T cells have specific antigens that target specific cancers
PD-L1 binds receptor to inhibit T-cell proliferation and activation

22
Q

What is Ipilimumab?

A

Acts at CTLA-4 receptors- cytotoxic T lymphocyte associated antigen 4

These block the inhibitory mechanism thought to allow cancer cells to survive

(CTLA-4 is somehow inhibited by tumor cells, these drugs block the inhibition)

23
Q

Indications for Ipilimumab?

A

Used in malignant melanoma

Enhances survival 4 months over standard therapy

24
Q

Side effects of Ipilimumab?

A 
Diarrhea
Swelling of the colon
Rash
Fatigue
FATAL IMMUNE REACTIONS because it basically takes the breaks off the immune system
25
Q

What is Nivolumab?

A

IgG4 fully human antibody, FDA approval Dec 2014

26
Q

What is Pembrozilumab?

A

IgG4 humanized antibody, FDA approved Sept 2014

27
Q

What are Nivolumab, Pembrozilumab used for?

A

Refractory advanced melanoma
NSCLC
Renal cell carcinoma
Hodgkin’s disease

28
Q

Adverse effects of Nivolumab, Pembrozilumab?

A 
Immune related pneumonitis
Hepatitis
Pancreatic vasculitis
Rash
Can have fatal immune reactions
29
Q

What is Sipuleucel-T?

A

A drug that is made from antigen presenting cells of the patient
You collect the antigen presenting cell from the patient, send them to the lab to be combined with prostatic acid phosphatase (found in 95% of cancer cells) then re-infuse it into the patient to cause immune response to cancer cells

Increases survival 4 months over controlled therapy

30
Q

Toxicities with Sipuleucel-T?

A 
Chills
Fatigue
Fever
Back pain
Infusion reactions
Stroke
31
Q

What are CAR T-Cells?

A

Chimeric antigen receptor T-cells

Modification of T-cells to express chimeric antigen receptors that recognize cancer specific antigens

32
Q

What are CART cells used for?

A

In clinical trials for ALL, CLL, and B cell lymphoma

Very high initial response rates above 80%

33
Q

What are the major side effects of CART cell therapy?

A

Cytokine (IL-6) release syndrome causing nausea, high fever, hypotension, respiratory arrest, and death

Less CRS in children

34
Q

What is D,L-asparaginase?

A

Asparagine is required for protein synthesis; normal cells take it up from the plasma and can synthesize

Lymphoid tumors have low levels of asparagine synthetase so they must take up asparagine

Aspariginase depletes asparagine in the plasma to decrease protein synthesis in tumor cells

35
Q

Indications for D,L aspariginase

A

Used in Childhood acute lymphocytic leukemia in combination with methotrexate, doxorubicin, and vincristine

(MTX must be given first because ASPase stops protein synthesis so it prevents MTX from working)

36
Q

Adverse effects of D,L asparaginase?

A 
Allergic reactions
Intracranial hemorrhage
Pancreatitis
Decreased clotting factors
Ammonia toxicity

Cology 2 Exam 4 (16 decks)

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