| abstract |
Prodn. of a cancer vaccine comprises culturing autologous tumour cells or fibroblasts, and then ex vivo transfection with a complex comprising: (1) DNA molecule (I) expressing at least one immunostimulating polypeptide (A), or several (I) encoding different (A), and opt. other DNA (II) not encoding a functional polypeptide; (2) a conjugate between a DNA binding cpd. (III) and endo-somolytic agent (IV), i.e. an adenovirus with a mutation at least in the E4 region; adenovirus that apart from a deflect in the ETa region has 1 or more additional genetic deflects or an endosomolytic peptide, and opt. (B) a DNA binding cpd. (IIIa), pref. conjugated to an internalisation factor that binds to a surface molecules on the cell being transfected components (1)-(3) form a practically electrically neutral complex. The transfected cells are inactivated to retain ability to express (I) but they cannot replicate. In the case of transfected fibroblasts, these are combined with inactivated but not transfected tumour cells, and the cells are opt. formulated with auxiliaries and carriers. Also new are (A) the vaccines themselves, (B) transfection complexes consisting of components (1), (2) and (3); (C) human tumour cells and fibroblasts transfected with such complexes. Each immunisation is with 0.1-10 million tumour cells, but when fibroblasts are transfected the no. can be reduced 100 fold. |