Cancer gene therapy with heat shock protein-65 gene.

Heat shock proteins (HSPs) are highly conserved proteins present in every living cell. Many members of the HSP family are essential for cellular functions under physiologic conditions, others are induced by various forms of cellular stress (including sudden increase in temperature) to protect cells from environmental damage (1,2). Involvement in protein folding and transport led to designation of HSPs as molecular chaperones (3).

In vivo gene therapy of malignant tumours with heat shock protein-65 gene.

We have previously shown that ex vivo insertion of a gene encoding the mycobacterial heat shock protein-65 into tumour cells results in their inability to form tumours in mice. We report regression of highly malignant reticulum cell sarcomas (J774) after liposome-mediated gene transfer in vivo. Heat shock gene transfer resulted in tumour regression both in immunocompetent and immunodeficient SCID mice. Complete tumour eradication, however, was detected only in immunocompetent animals, confirming the role of T cells in tumour rejection. Treatment of tumour bearing mice with the heat shock gene-liposome complex resulted in the production of antibodies against the tumour cells, indicating an increase in the antigenicity of the tumour after gene transfer. These results suggest that the heat shock protein-65 gene could provide a novel approach for the treatment of established tumours.