Einfluss des Immunisierungszeitpunktes und der Tumorlast bei der Immuntherapie des Mammakarzinoms mit Anti-Idiotypen-Antikörpern

Bislang ist die Immuntherapie noch nicht als eigenständige Therapie der ersten Wahl etabliert sondern wird zusätzlich zu konventionellen onkologischen Therapien angewendet. Die vorliegende Arbeit folgt der Immun-Netzwerk-Theorie von Nils Jerne, die von der Wirksamkeit einer Impfung mit anti-idiotyp...

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Bibliographic Details
Main Author: Schmidt-Nicolai, Sascha Thilo
Contributors: Wagner, Uwe (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2009
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Table of Contents: Immunological approaches using monoclonal antibodies in oncological treatment have been emerging during the last decades. In some fields antibodies yet implemented in standard therapy regiments. Our strategy follows the immunological-net-work-theory of Niels Jerne using an anti-idiotypic-antibody (Ab2) for active tumour vaccination. According to Niels Jernes theory the variable antigen-binding region of Ab2 represents the internal image of the tumour related antigen. An immunized organism creates anti-anti-idiotypic-antibodies (Ab3) witch cross-react with the original tumour-related- antigen. Immunisation with the Ab2 results in a specific immune reaction against the tumour. Worldwide, breast cancer is by far the most common cancer amongst women, with an incidence rate of 100/100000. In 2005, breast cancer caused 502,000 deaths worldwide. Mean age is 57 years. A single cause for developing a breast cancer is unknown, but until now individual, genetic and epidemiological risk factors are proven. Many of metastatic active breast cancers express a specific membrane polypeptide antigen described by De Potter et al. 1994 and Coene et al. 1997 as CA 14C5. This antigen is a polypeptide-adhesions-molecule of ductal carcinoma cells which seems to be involved in tumour invasions and adhesion. We created an anti-idiotypic-antibody ACA 14C5 mimickig the CA 14C5 and proved immunotherapeutic properties of this new Ab2 in 2 experimental settings in an established animal model with Balb/c mice. In the tumour last challenge (TLC) setting tumour implanted mice where immunized every week with 100μg ACA 14C5. The control-group according with 100μg mouse immunoglobuline (IgG). A second control-group received no treatment. 71,4 % of the antiidiotypic treated animals showed whether tumour remission or complete remission in comparison with immunisation with mouse-IgG or no therapy. In the prophylactic immunisation (PI) setting we showed that a immunisation before tumour implementation has a strong influence on tumour growth, according to the amount of tumour cells implanted. 14 days after immunisation with 100μg ACA 14C5 animals received tumour cells in three subgroups. 5, 10, and 25 million HH-16cl.2/1 fibrosarcoma cells where implanted. The lower the tumour-cell concentrations the better the in animal response. No tumour growth was observed in immunized animals which received 5 Mio. tumour cells. Immunisation with the anti-idiotipic-antibody ACA 14C5 represents a feasible approach in oncological treatment of breast cancer in an animal model. Still much more work has to be done to prove possible benefit in humans.