BIOLOGIC THERAPIES

Definition
The use of biologic materials, cells or cells

products, which acts directly on the cell proliferation or the cell differentiation or which modified the host response against the cancer cells. It can kill the cancer cells or stop their development or it can enhance the host immune response against the tumor (increasing the number or the efficacy of effective cells).

Products
Anti-proliferative alpha and beta interferon tumor growth factor beta stem cell inhibitors oncostatin Immunoactive products lymphocytes interleukines gamma interferon Tumor necrosis factor Monoclonal antibody

Products
Hematopoetic growth factors erythropoetin Granulocyte- colonies stimulator factors Granulocyte-macrophage colonies stimulator factors thrombopoetin hematopoetic stem cells Antimetastatic and antiangiogenic colagenase inhibitors platelet factor 4 trombospodin fumagillin

 Immunotherapy active
specific unspecific (local or systemic)

passive
antibodies active cells

Gene therapy

IMMUNOTHERAPY

Immune response
Afferent components T and B lymphocytes - recognize the malignant antigens Immune center lymphoid organs Efferent component active cells: T helper lymphocytes, cytotoxic T lymphocytes, natural killer cells, limfocite killer activated lymphocytes, tumor infiltrated lymphocytes, macrophages antibodies - produced by B lymphocytes cytokines - produced by lymphocytes and monocytes

Immunotherapy
This concept conceals very different

methods: partly scientifically proven therapies, but for the large part unproven and/or ineffective pseudo-treatments, which are commonly used under the label of additional therapy

Active immunotherapy
Principle - to determine an immune

response of the host against the tumor The results depend on the host immune capacity or on the tumor capacity to induce immune response

Unspecific active immunotherapy

local immediate immune response induced by local injection of a substance (bacterial derivated) examples intratumoral injections or intracavitary injections (bladder) (BCG, C. parvum, cytokines) systemic unspecific stimulation with interferon and/or inteleukin 2 (melanoma). Inflamatory reactions are induced either directly or via release of mediators (IL-6); these inflamatory reactions can also be directed against certain tumor cells.

Specific active immunotherapy

Vaccination with autologous or allogenic

tumor cells. The cellular surface of these cells are altered after infection with apathogenic viruses so that our immune system can recognize them, or these cells are prepared together with potent antigen-presenting cells (dendritic cells), and administered. The combination of both methods is already being tested in clinical trials under the designation ASI therapy (active specific therapy) (colon cancer stage II, III)

Specific active immunotherapy

The tumor capacity to express the antigens

is very important Vaccination with tumor-specific proteins leads to the induction of T-cell response, whereby no useful results have been achieved to date, and a dependency on certain HLA patterns limits administration

Passive immunotherapy
Administration of tumor cell-destroying

lymphocytes, which were expanded in vivo or in vitro (LAK = lymphokine-activated killer cells, TIL = tumor-infiltrating lymphocytes)

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 very important in the future because it is a main focus on endeavour in current scientific research.

Cytokines
interleukine interleukine 2 is used in renal cancer, malignant melanoma, other tumors (lymphoma, sarcoma, NSCLC, colorectal cancer) interferons interferon alpha used in renal cancer, malignant melanoma, leukemia (CML), lymphoma, carcinoids, Kaposi sarcoma Tumor necrosis factors used in malignant melanoma, sarcoma Growth factors used to permit higher chemotherapy doses

Monoclonal antibodies
Edrecolomab - colorectal cancer
Rituximab - CD20 expressing B-cell lymphoma Trastuzumab - Her2-neu over-expressing breast

cancer Bevacizumab - colorectal cancer

GENE THERAPY

Gene therapy
Only experimental use to date
Transfection of tumor cells (with

immunostimulating factors, eg IL-2, GMCSF) Introduction of suicide genes Changing the oncogenes (injection of p53) The path to clinical use is still long.