Flashcards in Immune System Stimulants Deck (12)
What are the two types of immune system stimulants?
2. Hematopoetic agents
What are the cytokines?
-Tumor Necrosis Factor Alpha
What are the common characteristics of cancer cytokines?
1. Short half-lives
2. Not cytotoxic by themselves --> they recruit immune cells to do the actual cell kill (immune system has to recognize tumor cells as foreign)
Despite their human origin, IL-2, IFN-alpha and TNF-alpha can have. . .
. . .serious, even fatal, side effects.
How does Interleukin-2 work?
-Not directly cytotoxic - induces and expands a T-cell response cytolytic for tumor cells
-Used either alone or with adoptive cellular therapy (LAK or CIK cells)
---Cells are produced by obtaining autologous lymphocytes, culturing them with x-irradiated tumor cells in the presence of IL-2 and then reinjecting them into the patient along with IL-2
-Short half-life (t1/2 = 13 minutes --> either continuously infused or given as multiple intermittent daily doses
What are the side effects of high doses of IL-2?
-Activation and expansion of lytic lymphocytes cases inflammation, vascular leak an secondary release of other cytokines (such as TNF, interferon alpha) = CYTOKINE STORM
-Can produce mild/moderate fever/chills, diarrhea and wight gain or hand-foot syndrome (palmar-plantar erythrodysestesia)
-Serious toxicities such as thrombocytopenia, shock, respiratory distress, coma and fatal hypotension
What are the three mechanisms of Interferon alpha?
1. Decreases production of fibroblast growth factor (FGF)
-anti-FGF actions may be responsible for actions against leukemic stem cells in chronic myeloid leukemia
-FGF is angiogenic
2. Inhibition of cell division of both normal and tumor cells
3. Increases class I MHC expression on tumor cells (actually restores normal MHC expression levels --> increased activity of cytotoxic T lymphocytes)
What side effects are associated with Interferon alpha?
-Flu-like symptoms: fever, arthralgia, headache, fatigue
What does tumor necrosis factor alpha do?
-Similar to IL-1 in terns of actions: causes fibroblast proliferation, chemokine induction (IL-6, IL-8), T and B cell activation
-Effect on many cell types (at least 17 different kinds) - causes a decrease in the rate of proliferation of tumor cells while sparing normal cells
-Intra-arterial administration due to extremely short half-life and toxicity.
-Sever dose-limiting toxicity is malaise and flu-like symptoms - can cause hemorrhagic necrosis
What immune system stimulants are hematopoietic agents?
Wha tis the dose-limiting complication of many antineoplastic drugs?
Bone marrow suppression