Terapia Biologica ENGL

7/30/2019 Terapia Biologica ENGL

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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.

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