No effective therapy against adrenocortical carcinoma (ACC) is currently available, as is the case for most other solid carcinomas. Recently, new promising therapeutic approaches have arisen, such as immunotherapy based dendritic cell vaccination or targeting the tumour stroma. However, the first clinical trials targeting the tumour stroma with antibodies or small molecules were disappointing. Additionally, it is widely accepted that one treatment modality is not sufficient to cure cancer.
The aim of this study is to combine two promising approaches, immunotherapy and stromal therapy into a novel approach whereby patients are vaccinated against products, which are preferentially over-expressed in the tumour stroma. Thus, we combine the advantages of a classical immunotherapy with targeting the tumour stroma, eliminating some of the inherent limitation of current antistromal strategy, offering an immunological treatment of minimal or no toxicity that should be applicable to almost all solid malignancies. Murine studies will test the hypothesis that an immunization with DC transfected with mRNA encoding tumour stroma antigens (e.g. FAP, MMP14) will inhibit tumour progression. In addition, synergistic effects of an immunotherapy targeting the tumour itself and the tumour stroma will be assessed. A preclinical in-vitro-study will test the capability to stimulate a specific cytotoxic T cell response in humans and will optimise the procedures clinical trials planned in patients with ACC.
The first host is one of the pioneers in the field of dendritic cell based immunotherapy, Prof Gilboa, Duke University, USA. The proposed methods are well established in his laboratory. The second host is Prof Allolio, University of Wuerzburg, Germany. He is one of the leading researchers in the field of adrenocortical carcinoma in Europe. This program will serve as a foundation for establishing a Europe-wide network of investigators to apply these concepts to a broad range of other cancers.
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