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
IL-2 Molecular Mechanisms
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
IL-2 Drug Mechanism
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)
IL-2 PK
Even shorter half-life than IFN (15-85 minutes)
Leaks into tissue upon injection
DO NOT vigorously shake because the proteins will degrade
IL-2 Indication
Adults Metastatic Renal Cell Carcinoma
Adults with Metastatic Melanoma
***IL-2 Clinical Condition Requirements
Normal cardiac and pulmonary test via thallium stress test
IL-2 Drug interaction
Nephrotoxic, myelotoxic, cardiotoxic, hepatoxic drugs
Glucocrticoids reduce side effects but also reduce antitumor effects
IL-2 Precautions
Normal cardiac and pulmonary function
Impaired neutrophils so increased risk of infection
Capillary leak syndrome
Define Capillary Leak Syndrome
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
IL-2 AE
HypOtension Pulmonary congestion Anemia Thrombocytopenia Capillary leak syndrome (pretty much leads to all the other AEs)
