Therapeutic Cytokines Flashcards
(24 cards)
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)
