Immune altering and Hormonal therapy - Slides 1-22 Flashcards
How are tumor cells different than normal cells when it comes to our immune system?
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
What is interferon alpha? How does it work?
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
What types of Interferon alpha are they? How are they different?
Alpha 2A - Roferon-A - Lysine 23
Alpha 2B - Intron-A - Lysine 23
Indications for interferon alpha?
Hairy cell leukemia Kaposi's sarcoma CML Chronic Hep B Malignant melanoma Multiple sclerosis
How is Interferon alpha administered?
SubQ multiple times weekly up to 12 months
Adverse effects of Interferon alpha?
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
True or False: Interferon alpha is safe in pregnancy
False - can pass to fetus
No breast feeding either
What is Interferon B used for? What types are there?
Relapsing multiple sclerosis
Interferon B-1-a (166 aa)
Interferon B-1-b (165 aa)
What is interferon gamma? How does it work?
Interferon gamma-1b
Activates phagocytes, increases oxygen radicals
Indications for interferon gamma?
Prevents serious infections in chronic granulomateous disease (inherited immunodeficiency)
Toxicities for interferon gamma?
Flu like syndrome
GI distress
Weight loss
Depression
What is Aldesleukin?
It is an interleukin
Interleukins serve as molecular messengers between leukocytes
How many interleukins do humans have?
17
Aldesleukin MOA
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
How is Aldesleukin administered?
IV or infusion for 5 day cycles with 5-9 days between cycles
Aldesleukin indications
Metastatic renal cell carcinoma
Metastatic melanoma
Colorectal cancer
Malignant lymphoma
Adverse effects of Aldesleukin
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
Cautions with Aldesleukin
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
How do Immune Checkpoint Blockers work?
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
What is CTLA-4?
Cytotoxic T-lymphocyte associated antigen-4, released by activated T-cells to dampen immune response
What is PD-1?
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
What is Ipilimumab?
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)
Indications for Ipilimumab?
Used in malignant melanoma
Enhances survival 4 months over standard therapy
Side effects of Ipilimumab?
Diarrhea Swelling of the colon Rash Fatigue FATAL IMMUNE REACTIONS because it basically takes the breaks off the immune system
What is Nivolumab?
IgG4 fully human antibody, FDA approval Dec 2014
What is Pembrozilumab?
IgG4 humanized antibody, FDA approved Sept 2014
What are Nivolumab, Pembrozilumab used for?
Refractory advanced melanoma
NSCLC
Renal cell carcinoma
Hodgkin’s disease
Adverse effects of Nivolumab, Pembrozilumab?
Immune related pneumonitis Hepatitis Pancreatic vasculitis Rash Can have fatal immune reactions
What is Sipuleucel-T?
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
Toxicities with Sipuleucel-T?
Chills Fatigue Fever Back pain Infusion reactions Stroke
What are CAR T-Cells?
Chimeric antigen receptor T-cells
Modification of T-cells to express chimeric antigen receptors that recognize cancer specific antigens
What are CART cells used for?
In clinical trials for ALL, CLL, and B cell lymphoma
Very high initial response rates above 80%
What are the major side effects of CART cell therapy?
Cytokine (IL-6) release syndrome causing nausea, high fever, hypotension, respiratory arrest, and death
Less CRS in children
What is D,L-asparaginase?
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
Indications for D,L aspariginase
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)
Adverse effects of D,L asparaginase?
Allergic reactions Intracranial hemorrhage Pancreatitis Decreased clotting factors Ammonia toxicity
