Effektivitätsanalyse eines in vivo Depotsystems zur Langzeitsekretion von anti-idiotypischen Antikörpern für das Tumor assoziierte Antigen CA125

Ovarialkarzinome sind die häufigste Todesursache durch gynäkologische Malignome in den USA und Deutschland. Aufgrund der Symptomarmut zu Beginn der Erkrankung sowie das Fehlen sufizienter Frühscreeningsmethoden werden über 70% der Ovarialkarzinome in einem fortgeschrittenen Stadium diagnostiziert. T...

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Bibliographic Details
Main Author: Hann, Evelin
Contributors: Wagner, Uwe (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2011
Online Access:PDF Full Text
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Ovarian cancer represents the third most common malignancy of the genital tract. Because more than 50% of ovarian cancer patients are stage III and 20 % are stage IV at the time of diagnosis, this tumour is associated with an extremely unfavourable prognosis. Because the success of chemotherapy regiments after failure of first-line therapy is limited, the development of other therapeutically methods e.g. immunotherapy became necessary. One promising application in ovarian cancer immunotherapy is the administration of the murine anti-idiotypic antibody abagovomab that imitates the tumour-associated antigen CA 125, which is overexpressed by about 80 % of ovarian carcinomas. Abagovomab is currently being tested in a Phase II/III trial in ovarian cancer patients with a complete response after standard first-line chemotherapy. Activating the cancer hosts immune system via an anti-idiotypic network system is a new strategy that is worth being pursued in the fight against ovarian cancer. A drawback of abagovomab is its low immunogenicity. The goal of the present work was to determine if a continuous delivery system for abagovomab will show an advantage over conventional immunization in inducing a durable antitumor response. Based on bioencapsulation technologies, we generated in a previous work a cell culture system that acts as a continuous delivery system for the abagovomab derivative ACA125hFc and concluded that recombinant C2C12 myoblasts encapsulated in semi permeable hollow fibers can be employed as secretion devices for this antibody. In the present work we developed an allogene mouse model, acting as a long term delivery system for ACA125hFc expressing allografts. Compared with conventional anti-idiotypic immunization the new antibody application systems showed a significant improvement in humoral as well as in cellular immune responses. Further studies using e.g. ovarian cancer animal models will show if this new delivery system is able to improve the anti-tumoral response against CA125.