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BIOLOGIC THERAPIES
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Definition
The use of biologic materials, cells or cellsproducts, which acts directly on the cellproliferation or the cell differentiation or
which modified the host response againstthe cancer cells.
It can kill the cancer cells or stop their
development or it can enhance the hostimmune response against the tumor(increasing the number or the efficacy ofeffective cells).
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Products
Anti-proliferativealpha and beta interferon
tumor growth factor beta
stem cell inhibitorsoncostatin
Immunoactive productslymphocytes
interleukinesgamma interferon
Tumor necrosis factor
Monoclonal antibody
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Products
Hematopoetic growth factorserythropoetin
Granulocyte- colonies stimulator factors
Granulocyte-macrophage colonies stimulatorfactors
thrombopoetin
hematopoetic stem cells
Antimetastatic and antiangiogeniccolagenase inhibitors
platelet factor 4
trombospodin
fumagillin
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Immunotherapy
active
specific unspecific (local or systemic)
passive
antibodies
active cells
Gene therapy
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IMMUNOTHERAPY
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Immune response
Afferent componentsT and B lymphocytes - recognize the malignant
antigens
Immune center
lymphoid organs
Efferent componentactive cells: T helper lymphocytes, cytotoxic T
lymphocytes, natural killer cells, limfocite killer
activated lymphocytes, tumor infiltratedlymphocytes, macrophages
antibodies - produced by B lymphocytes
cytokines - produced by lymphocytes and
monocytes
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Immunotherapy
This concept conceals very different
methods: partly scientifically proven
therapies, but for the large part unprovenand/or ineffective pseudo-treatments, which
are commonly used under the label of
additional therapy
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Active immunotherapy
Principle - to determine an immune
response of the host against the tumor
The results depend on the host immunecapacity or on the tumor capacity to induce
immune response
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Unspecific active immunotherapy
localimmediate immune response induced by local
injection of a substance (bacterial derivated)
examples intratumoral injections or intracavitaryinjections (bladder) (BCG, C. parvum,cytokines)
systemicunspecific stimulation with interferon and/or
inteleukin 2 (melanoma). Inflamatory reactionsare induced either directly or via release ofmediators (IL-6); these inflamatory reactions canalso be directed against certain tumor cells.
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Specific active immunotherapy
Vaccination with autologous or allogenictumor cells.
The cellular surface of these cells are alteredafter infection with apathogenic viruses sothat our immune system can recognize them,or these cells are prepared together withpotent antigen-presenting cells (dendriticcells), and administered. The combination ofboth methods is already being tested inclinical trials under the designation ASItherapy (active specific therapy) (coloncancer stage II, III)
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Specific active immunotherapy
The tumor capacity to express the antigens
is very important
Vaccination with tumor-specific proteinsleads to the induction of T-cell response,
whereby no useful results have been
achieved to date, and a dependency oncertain HLA patterns limits administration
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Passive immunotherapy
Administration of tumor cell-destroying
lymphocytes, which were expanded in vivo
or in vitro (LAK = lymphokine-activatedkiller cells, TIL = tumor-infiltrating
lymphocytes)
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Passive immunotherapy
Administration of antibodies against tumor-
specific antigens. These antibodies either
have a direct cytotoxic effect, or induce a
specific immune response via anti-idiotypic
antibodies, or indirectly inhibit cell division
by blocking growth-factor signals.
This form of therapy may become veryimportant in the future because it is a main
focus on endeavour in current scientific
research.
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Cytokines
interleukineinterleukine 2 is used in renal cancer, malignant
melanoma, other tumors (lymphoma, sarcoma,NSCLC, colorectal cancer)
interferonsinterferon alpha used in renal cancer, malignant
melanoma, leukemia (CML), lymphoma,carcinoids, Kaposi sarcoma
Tumor necrosis factorsused in malignant melanoma, sarcoma
Growth factorsused to permit higher chemotherapy doses
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Monoclonal antibodies
Edrecolomab - colorectal cancer
Rituximab - CD20 expressing B-cell lymphoma
Trastuzumab - Her2-neu over-expressing breast
cancer
Bevacizumab - colorectal cancer
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GENE THERAPY
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Gene therapy
Only experimental use to date
Transfection of tumor cells (with
immunostimulating factors, eg IL-2, GM-CSF)
Introduction of suicide genes
Changing the oncogenes (injection of p53)The path to clinical use is still long.