Zatloukal, Kurt; Schmidt, Walter; Cotten, Matt; Wagner, Ernst; Stingl, Georg; Birnstiel, Max L.
Somatic gene therapy for cancer. The utility of transferrinfection in generating ‘tumor vaccines’.
In: Gene, Vol. 135, No. 1-2: pp. 199-207
The last few years have seen the development of a branch of somatic gene therapy which aims at strengthening the immune surveillance of the body, leading to eradication of disseminated cancer tumor cells and occult micrometastases after surgical removal of the primary tumor. Such a tumor vaccination protocol calls for cultivation of the primary tumor tissue and the insertion of one of three types of genes into the isolated cultured tumor cells followed by irradiation of the transfected or transduced cells to render them incapable of further proliferation. The cells so treated constitute the ‘tumor vaccine’. A review of the literature suggests that for mouse models, in the initial period after inoculation, rejection of the tumor cells is usually effected by non-T-cell immunity, whereas the long-term systemic immune response is based on cytotoxic T-cells. High expression of the gene inserted into the tumor cells may be critical for the success of the vaccination procedure. Examples are given which indicate that transferrinfection, a procedure to introduce genes by adenovirus-augmented receptor-mediated endocytosis, meets some important prerequisites for successful application of this type of gene therapy.