Immune altering and Hormonal therapy - Slides 1-22

Question 1

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

Answer 1

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

Question 2

What is interferon alpha? How does it work?

Answer 2

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

Question 3

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

Answer 3

Alpha 2A - Roferon-A - Lysine 23

Alpha 2B - Intron-A - Lysine 23

Question 4

Indications for interferon alpha?

Answer 4

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

Question 5

How is Interferon alpha administered?

Answer 5

SubQ multiple times weekly up to 12 months

Question 6

Adverse effects of Interferon alpha?

Answer 6

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

Question 7

True or False: Interferon alpha is safe in pregnancy

Answer 7

False - can pass to fetus

No breast feeding either

Question 8

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

Answer 8

Relapsing multiple sclerosis

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

Question 9

What is interferon gamma? How does it work?

Answer 9

Interferon gamma-1b

Activates phagocytes, increases oxygen radicals

Question 10

Indications for interferon gamma?

Answer 10

Prevents serious infections in chronic granulomateous disease (inherited immunodeficiency)

Question 11

Toxicities for interferon gamma?

Answer 11

Flu like syndrome
GI distress
Weight loss
Depression

Question 12

What is Aldesleukin?

Answer 12

It is an interleukin

Interleukins serve as molecular messengers between leukocytes

Question 13

How many interleukins do humans have?

Answer 13

17

Question 14

Aldesleukin MOA

Answer 14

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

Question 15

How is Aldesleukin administered?

Answer 15

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

Question 16

Aldesleukin indications

Answer 16

Metastatic renal cell carcinoma
Metastatic melanoma
Colorectal cancer
Malignant lymphoma

Question 17

Adverse effects of Aldesleukin

Answer 17

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

Question 18

Cautions with Aldesleukin

Answer 18

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

Question 19

How do Immune Checkpoint Blockers work?

Answer 19

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

Question 20

What is CTLA-4?

Answer 20

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

Question 21

What is PD-1?

Answer 21

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

Question 22

What is Ipilimumab?

Answer 22

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)

Question 23

Indications for Ipilimumab?

Answer 23

Used in malignant melanoma

Enhances survival 4 months over standard therapy

Question 24

Side effects of Ipilimumab?

Answer 24

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

Question 25

What is Nivolumab?

Answer 25

IgG4 fully human antibody, FDA approval Dec 2014

Question 26

What is Pembrozilumab?

Answer 26

IgG4 humanized antibody, FDA approved Sept 2014

Question 27

What are Nivolumab, Pembrozilumab used for?

Answer 27

Refractory advanced melanoma NSCLC Renal cell carcinoma Hodgkin's disease

Question 28

Adverse effects of Nivolumab, Pembrozilumab?

Answer 28

``` Immune related pneumonitis Hepatitis Pancreatic vasculitis Rash Can have fatal immune reactions ```

Question 29

What is Sipuleucel-T?

Answer 29

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

Question 30

Toxicities with Sipuleucel-T?

Answer 30

``` Chills Fatigue Fever Back pain Infusion reactions Stroke ```

Question 31

What are CAR T-Cells?

Answer 31

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

Question 32

What are CART cells used for?

Answer 32

In clinical trials for ALL, CLL, and B cell lymphoma | Very high initial response rates above 80%

Question 33

What are the major side effects of CART cell therapy?

Answer 33

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

Question 34

What is D,L-asparaginase?

Answer 34

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

Question 35

Indications for D,L aspariginase

Answer 35

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)

Question 36

Adverse effects of D,L asparaginase?

Answer 36

``` Allergic reactions Intracranial hemorrhage Pancreatitis Decreased clotting factors Ammonia toxicity ```