Therapeutic Cytokines Flashcards
Define Monoclonal Antibodies
Immunoglobulin designed to target oncoproteins expressed by tumor cells and to cause an immune response that destroys cancer cells (Targeted Therapy).
Define Adoptive T Cell Transfer
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.
Define Immunoregulatory Cytokines
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.
Define Treatment Vaccines
Antigen-presenting cells (APC) with PAP/GM-CSF as the vaccine active component to stimulate immune response against cancer
Define BCG
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.
Define Interferons
Cytokine produced by the cells of the immune system (T/B cells)
Type 1 Interferon
IFN-α, IFN-β
Type II Inferferon
IFN-γ
Mechanisms of IFN-α activation
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
Potential MOA of IFN in Tumor Therapy
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.
Pharmacokinetics of IFN
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
IFN Indications
o Ph+ CML o Hairy cell leukemia o Follicular lymphoma o AIDS-related Kaposi’s sarcoma o Malignant melanoma
IFN Acute AE
Flu-like: fever, headache, chills
IFN Chronic AE
Depression and suicidality
Fatigue and weakness
Incomplete Reiter’s Syndrome (deep ulcers on the tongue)
***Do NOT use IFN-α if:
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