Compositions and methods for dendritic cell-based immunotherapy
View Patent ↗Disclosed are immunostimulatory fusion proteins and methods for generating protective DC-induced, T cell-mediated immune responses in vitro and in vivo. The immunostimulatory fusion proteins comprise a polypeptide antigen component and an immunostimulatory component derived from the intracellular domain of the HER-2 protein. Also disclosed are immunostimulatory compositions comprising dendritic cells pulsed with such an immunostimulatory fusion protein and methods for immunotherapy using the compositions.
1. An immunostimulatory HER-2 fusion protein comprising:
a polypeptide or protein antigen sequence component and a sequence component derived from the intracellular domain of the HER-2 protein, said fusion protein is selected from the group consisting of HER500 (SEQ ID NO: 1), HER500•hGM-CSF (SEQ ID NO: 2), HER500* (SEQ ID NO:3) and HER500*•rGM-CSF (SEQ ID NO: 4), where said fusion protein is effective to elicit a cellular immune response to the polypeptide or protein antigen sequence component of the fusion protein.
2. The immunostimulatory HER-2 fusion protein of claim 1 , where the fusion protein is HER500•hGM-CSF (SEQ ID NO: 2).
3. A method of producing superactivated DC, by exposure to an immunostimulatory fusion protein, comprising:
exposing a dendritic cell (DC) or dendritic cell precursor (DCP) to the immunostimulatory fusion protein of claim 1 , in a manner effective to result in a cellular immune response to the polypeptide or protein antigen sequence component of the fusion protein.
4. The method of claim 3 , where said exposing takes place in vitro.
5. The method of claim 3 , where said exposing takes place in vivo.